Urea recyclittg in active golden-mantled ground squirrels

7/29/2019 Urea recyclittg in active golden-mantled ground squirrels

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SEeffen, J. M., G. L. Rigler, A. K. Moore and M. L. Riedesel.1980. Urea recycling in active golden-mantled ground squirrels(Spermophilus laleralis). An. J. Physiol. 2392 R16B-R173(Regulatory Integrative Comp. Physiol. B)Urea recyclittg in active golden-mantled ground squirrels

srrrrnN, J. M., G' L' Rrcr,rn, A. K. Moonn, aNo M. L. squirrel differ liom the bear in a number of respects,Rrnoosnr,. (Jrea recycling in actiue golden-mantled ground such as energy reserves and depth of torpor. The depthsquirrels (spermophilus lateralis)' Am' J' Phvli-o-I 2l?ll"ry- oilo.por in the ground squirrel permits little or no renall1|T"JT?:l"il:3,:.tdl:111":! *,1."--*:li"JixhT lt;q;" fo, p",ioaJoi6;" 3 wk (21, 28). rt,therefore,urine urea excretiin decline"d .nutpry i" no;ilffiil *.;;; may be argued that in the hibernating ground squirrel,squirrels (Spermophilus tateralisf *n"" .o-fu."J ;rtf,-hb;: urea cannot be excreted and must be stored or recycled.ratory-rats. Intraperitoneal injection of urea "qui"J""t to o.iZ Fasted and fasted water-deprived normothermic lquir-of body weight failed to increase blood urea in l2-h fasted rels likewise exhibit limited urine excretion (3). Conflict-ground squirrels, and led to littie urine urea excretion when ing reports concerning plasma urea levels in a number ofcompared with similarly tieated rats. Collection.of expired Co2 hibernating sciurids [f ia, f e , 26) do not permil quanti-fromfastedorfastedwater-deprivedgroundsquirrelsihatwere tative evaluation of the role'of protein ir"tuUl1r,,' o,urea loaded and injected with a tracer dose oi taC-tagged urea urea recycling during hibernation. However, observationsrevealed a 1'000- to 1'500-fold gteater 'nco, ex.pitaiion than "" u"trr hibernating marmots (1) and arctic ground squir-iiill,i"li;,lliilfi:::.":"1?H;HiliiJi:lantibiotics (peni- '"i. jrsl reveat th-at urea excretion durin! intertorporcroflora reduced expired ,,co, to control t"""t.. i;?:!|!.f*n- no^rm'othermia underestimates loss of lean body mass byrels, drug tr"ut'''"nt also enhanced wine ".", ;;;;;;;;;ilir",h a factor of seven.values approaching those of controls. The results "i tt """ Urea nitrogen recycling via bacterial urease is wellexperiments point to the possibility of urea nitrogen recycling documented in ruminants (6). Urea and ammonia nitro-in nutritiona,v srressed ground squirrers. " i:ffi::::'Jg"itr#il""hruffi,:li:Tl"S,:Tl"A"riT*:urea metabolism; nitrogen ba-lance; intestinal microflora; fast- rabbits (27), and swine (10). Conflicting reports haverng; n)?ophagra appeared concerning recycling ofurea carbon (18,27). InWHEN CONFRONTED with the reduced food and free water nitrogen balance.availability of the winter season, the golden-mantled This study was underbaken to i) monitor urine ureaground squirrel(Spermophilus lateralis) enters a period excretion in fasted and fasted water-deprived groundof hibernation during which energy is supplied from squirrels, il) determine the response to urla loadiirg, lil)stored triglycerides (15,22). Summei-active animals, in quantitate the metabolism of [1aC]urea, and iu) iete/-contrast, respond to food and water deprivation with a mine urea excretion following administration of micro-marked increase in protein catabolism (2i, which, coupled flora-reducing antibiotics.with reduced evaporative (4) and urinary water ioss,serves to maintain positive water balan"". Aa a result, MATERIALS AND METHODSwith reduced urine volume, enhanced production of ni. Laboratory rats of both sexes were obtained from thetrogenous wastes such as urea, and with only moderate Holtzman Clmpany, Madison, WI. Ground squirrels ofurine-concent-rating abilities (5),the ground squirrel must both sexes were captured with Sh"t;;;;;upi1"t*""r,exhibit a mechanism(s) for ameliorating the iubsequent 2,550 and 3,300 m i.r tn" Jemez mountains of norther'uremia which would be expected to develop. New Mexico, and experiments conducted S-24 mo after, UIgu recycling has been reported in one hibernator, capture. All animals were caged singly, provided withthe.black bear (Ursus ame1icanu:), by Nelson and co- *ut"r, and fed commercial rat chow (2I7o protein) sup-workers (see Ref. 23fo.t review). Theyobserved no loss plemented with fresh vegetables. Animal quarters wereof .lean body mass during the period of hibernation de- maintained at 28 + B'C ;ith a natural tigh; ctcle.spite the continued production of urea (24) . ln addition The first series of experiments examined urea excretionthey noted l) urea was reabsorbed from the bladder at a after deprivation of iood, water, or both in differentrate equivalent to its rate of excretion by the kidney (24); ""u"o.,". Rats were fasted and water deprived (FWD) forii) blood urea levels remained unchanged during rrin"r- 6 days in December. Ground squirrels *ere pWn in bothnation (25); and jjl) intestinal storage 6f urea- cJuld not Ma5iand December. A third group of squirrels was fastedbe demonstrated (25)' Hibernators such as the ground for ? auyr during fufuv tr,ro"sh Julv. Urine was collected

(Sp ermophilus later atis)J. M. STEFFEN, G. L. RIGLER, A. K. MOORE, AND M. L. RIEDESELDepartment of Biology, (Jniuersity of New Mexico, Albuquerque, New Mexico gz1sl

both normothermic and hibernating anirnals the intes-tinal flora may make a significant contribution to overall

Rl68 0363-6119/80/0000-0000901.25 cop5a'ight o 1980 the American physiological Society


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UREA RECYCLING IN ACTIVE GROUND SQUIRRELS

CO2Tmp NoOHLiquid TmpScintilhioaCochtoilrrc. 1. Chamber for collection of urine and expired 'aCOz.

under oil in large watch glasses placed beneath wire meshcages. Once daily, urine was pipetted from beneath theoil and refrigerated (1-5 days) in tightly capped vials.Duplicate urea analyses on fresh and stored samples weresimilar. Urea analyses were made by a diacetylmonoximeand thiosemicarbazide colorimetric method (8), which isnot sensitive to ammonia, creatinine, or amino acids.Blood and urine urea were measured after urea loadingin a second series of experiments. Ground squirrels (166-222 d and rats (366-466 g) received an intraperitoneal(ip) injection of urea equal to 0.37o of body weight. Ureawas delivered, in all cases, in 2 ml of aqueous solutionafter the animals had been fasted for 12 h. An objectiveof this experiment was to test the effects of urea loadingon fasted animals with water available. Because leakagefrom water bottles into the cage and urine-collectingvessels can give elroneous measurements of urine vol-ume, raw potato ad libitum was the single source of waterthroughout the experiment. The nutrient content of thepotato consumed represented 9-237o of the resting met-abolic rate of the animals and therefore the animals wereconsidered to be in a fasting condition. The mean waterintake was 4.7 and 9.4 g per 36 h by ground squirrels andrats, respectively. Blood samples were obtained by tailclipping. Urine was collected and urea content of bloodand urine was analyzed as above.Metabolism of [lnC]urea was investigated in animalsfollowing a single 2-ml ip injection of an aqueous solutioncontaining 0.3 g unlabeled urea per 100 g body weightand 10 pCi ['nC]urea. After injection, animals weie plaiedin a 1.25-liter chamber (Fig. 1). Air, 100-200 ml/min,entered the chamber after passing through a COz trap of2.5 N NaOH. Upon exit from the chamber, the air passedthrough two solutions containing a COz-trapping scintil-Iation cocktail and a final 2.5 N NaOH trap to preventcontamination of laboratory air. The COz- trapping scin-tillation cocktail consisted of 0.5Vo (wtlvol) 2,S-diphen-yloxazole (PPO), 55Vo (vol/vol) toluene, 39Vo (vol/vol)ethylene glycol monomethyl ether, and, 5.5Vo (vollvol)ethanolamine. Aliquots of each CO2 trap and urine sam-ples were removed after 24 h. A 0.25-ml aliquot of urinewas transfened to a counting vial along with 3 ml of NCSsolubilizer, and the total volume increased to 18 ml bythe addition of 0.5Vo PPO-toluene cocktail in preparationfor counting. The CO2 trap and urine samples werecounted in a Beckman LS-100 liquid scintillation counter.Control animals were allowed free access to food andwater prior to urea administration. Fasted animals, as

R169well as FWD and drug-treated FWD animals, had anaverage 25Vo weight loss prior to urea administration.For comparison of tnCO2 production with urine 1aCelimination in ground squirrels, a separate experimentinvolved animals fasted for 4 days with water withheldfor the final day of the fast. Groups of these animals weredrug treated (FDT) according to one of the followingprotocols; i) 500,000 IU procaine penicillin G intramus-cularly 36 h prior to administration of urea, ii) 0.027osulfamethazine in the drinking water for 4 days prior tourea administration; iii) 5 ml tetracycline (1.0 g/100 rnlwater) by gavage given in two equal doses 24 h and 8 hprior to urea administration.An additional experiment involved monitoring ureaexcretion following drug treatment. Control animals re-ceived food and water ad libitum. Fasted and FDT squir-rels received water ad libitum. The FDT animals received0.027o sulfamethazine in the drinking water. Urine collec-tion and urea analyses were as above.The ['4C]urea (60 mCi/mmol), PPO, toluene, and NCSsolubilizer were obtained from Amersham/Searle; ethyl-ene glycol monomethyl ether and ethanolamine werefrom Sigma; sodium sulfamethazine and tetracycline-HClwere from American Cyanamid; procaine penicillin G(Streptillin) was from Pfrzer.Data were analyzed by the Student's f test and the nullhypothesis was rejected at the SToIevel ofconfidence.RESI,JLTS

The excretion of urea is altered following water depri-vation and./ or fasting of laboratory rats and ground squir-rels. Within 3 days, FWD rats had reduced urea excretionby 46Vo (Fig. 2). Extension of the period of deprivation to6 days was accompanied by increased daily urea output.The FWD ground squirrels during both May and Decem-ber, as well as summer-fasted squirrels, also had an initial

o123456DAYSrrc. 2. Seasonai effects of fasting or fasting and water deprivation(FWD) on daily urea excretion. FWD rats (Dec.) H; FWD groundsquirrels (May) fH; FWD ground squirrels (Dec.) H; fastedground squirrels (May-July) H). Vertical /izes represent SEM.

(5= 600O sooff oooFuJdQ sooIJJfi 2ooE:)


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R170depression in urea excretion, but to a greater extent (62,72, and 62Vo, respectively) than did the rats. Reducedurea excretion was maintained in ground squirrels evenwith extension of deprivation to 6 days. trt should benoted that simultaneous food and water deprivation, orfasting alone, induces similar trends in urea excretion.In an attempt to elucidate the mechanism underlyingthese differences in urea excretion, blood and urine ureawere monitored in rats and ground squirrels subjected toan exogenous urea load. Prior to urea loading, groundsquirrels had a higher blood urea concentration than rats(Fig. 3). Within 6 h of the injection, blood urea levels inthe rat had risen threefold, whereas the ground squirrelsresponded with little or no change in blood urea. In therat, blood urea levels fell to base line within 24 h. Incontrast, values for the ground squirrels were maintainedbelow those at time 0 for the remainder of the experi-ment. Thus, an ip urea load in the squirrel does not leadto short-term accumulation of urea in the blood.A greater renal efficiency in the removal of urea fromthe plasma may have accounted for the ground squirrel'sIack of short-term blood urea accumulation. Urine urealevels presented in Fig. 4 show that this was not the case.Ground squirrels excreted urea at or below the levels ofthe rats on a body weight basis for 48 h following urealoading. The results presented in Figs. 3 and 4 lead to theconclusion that, in S. lateralis, not all urea produced orinjected may actually be excreted; and, therefore, a lowrate of urea excretion in the squirrel (Fig. 2) rnay notnecessarily imply a low rate of urea production.A tracer dose of [tnC]urea was administered to urea-loaded animals to investigate the possibility that speciesdifferences in the capability for either tissue storage,metabolism, or both may account for the failure of theexogenous urea load to appear to a similar extent in the

FIOIJRSrrc. 3. Time course of blood urea changes following urea loading.Vertical lizes represent SEM.

STEFFEN, RIGLER, MOORE, AND RIEDESEL

=.9c,;En(t8gtrJzElz_lrj5-)F

].torJRsrrc. 4. Time course of urine urea excretion following urea loadingVertical lines represent SEM.rABLE 1. Twenty-four hour laCOz (dpm) expired bycontrol, fasted, and FWD rats and ground squirrels

Laboratory Rat Ground Squinel

col- Fastedtrolcol FastedrrolMean 103 183 273 262-fsE +14 +74 +22 !42n7775

Fastedwater-de-privedFastedwater-de-prived

3olsflE.loIICD

280,000 400,000+10,000 +15,00055FWD, fasted water-deprived.

blood and urine ofthe ground squirrels and rats. Fastedor FWD rats responded with nearly two- to threefoldincreases in tnCOz collected (Table 1), indicating onlyslight catabolism ofthe injected tracer. In contrast, fastedand FWD ground squirrels increased laCOz production1,000- to 1,500-fold. Thus, the capability for increasedurea catabolism would appear to be a component of themetabolic response to reduced food and water intake inthe ground squirrel.The extent of catabolism of urea in the ground squirrelis demonstrated in Table 2. Control squirrels excretedthe great majority of the injected 14C in the urine within24 h. Elimination of the tracer via catabolism is slight.Approximately 20Vo of the label is retained for at least 24h. A 4-day fast coupled with 24 h of water deprivationresulted in an 8-fold reduction in urine volume whereas14C elimination in the urine was decreased 30-fold. Thiswas accompanied by a l0-fold increase in the amount ofurea carbon in expired air. Whole body retention of thetracer also increased to approximately TOVo of the injecteddose. Treatment with penicillin, sulfamethazine, or tet-racycline resulted in decreased urea catabolism withvalues approximating those of controls (Table 2).In an effort to describe a potential direct relationship

C ffiUND flJlffiLo TA8 RAT


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UREA RECYCLING IN ACTIVE GROUND SQUIRRELSrABLE 2. Percentage of injectedraC collected inurine and expired air in control, FWD, andFDT ground squirrels

Twenty- Percentage of Injected trCfour-hour Collected in 24 hljrine Volume, ml COz trapControl (n : 9)Fasted water-deprived (n : 8)

+ peniciliin (n : 5)+ sulfa (z = 4)+ tetracycline (z:3)8.9 r 0.7 79 ! 4.4 2.4 + 0.151.1 + 0.7 2.6 -f 0.80 26.5 + 0.80

7.3 + 0.94.4 -r 1.21.4 t 0.6Values ale mean t SE. FWD, fasted water-deprived; FDT, fastedwater-deprived, drug-treated.

between urea recycling and intestinal microflora, ureaexcretion was monitored in control, fasted, and FDTsquinels receiving water ad libitum. Urea excretion inthe fasted animals declined progressively throughout the7-day fast (Fig. 5). The FDT squi-rrels, on the other hand,maintained urea excretion above the levels of the fastedanimals, being2.7 times greater by the 7th day'These same data are expressed on the basis of bodyweight in Fig. 6. Fasted squirrels reveal a progressivedecline in urea excretion over the length ofthe fast. Ureaelimination by the FDT squirrels remains close to thatof the fasted squirrels for the first 4 days of the fast. Thefollowing 3 days reveal an increase (P < 0.001 for day 7,P < 0.01 for days 5 and 6) in urea excretion by the FDTsquirrels over that of the fasted animals.DISCUSSION

Mobilization of lipid reserves as a fueI source, with aconsequent sparing or conseryation of protein, has beenrecognized as a nearly universal response to fasting. Thisadaptation is enhanced by the high caloric value of fatper unit mass and the ability of considerable portions ofthe nervous system to convert from a carbohydrate-basedmetabolism to the utilization of lipid intermediates. Thisselective lipid catabolism significantly prolongs the du-ration of fasting which an organism may tolerate. Theinitial depression of urinary urea excretion by FWD rats(Fig. 2) is consistent with the above proposal. Bintz et al'(2) have reported respiratory quotients indicative oflipidmetabolism in similarly stressed rats. Millward et al. (19)report a decrease in muscle protein catabolism in similarsized rats aftet 2 days c;f fasting though there is anincreased protein fractional turnover following 4 days offasting. There are indications that less mature rats maynot show a like response (17).The marked increase in urea excretion seen after 3days of fasting may reflect a substantial depletion of lipidreserves and a greater dependence on protein as a sourceof energy. 'ftre 20-25Vo body weight loss seen in these ratsover the fust 3 days of fasting may represent catabolismof most of the lipid reserves. The work of Cuendet et al.(9) on lean and obese mice would suggest that bodyprotein is spared until triglyceride stores have been seri-ously depleted. The buildup of urea in the blood followingurea loading (Fig. 3), its excretion (Fig. 4), and lack ofsignificant release of laCOz (Table 1) clearly indicates

R171that urea is treated primarily as a waste product in thelaboratory rat.Fasted and FWD ground squirrels, like the laboratoryrat, exhibit an initial decrease in urea excretion, but withtwo important distinctions, namely: i) the depression ofurea excretion is more pronounced (62-72Vo vs. 467o fotthe rat), and li) there is no follow-up increase in ureaexcretion upon extension of the duration of the fast.Bintz et aI. (2) reported S. laterolis preferentially catab-olizes protein under the same conditions of stress. Theseconflicting findings may be accounted for, in part, by theresponse of the ground squirrel to urea loading. It isevident that the movement of urea into the plasma inthe squirrel nearly balances its removal in view of thestability of plasma urea concentrations (Fig. 3) followingurea loading. In fact, plasma urea concentrations actually

5 loterolisCmrolElfFoded IFDI @

rrc. 5. Effect of fasting orlFDT) on daily urea excretion.34567

Doys of Fostirgfasting combined with drug treatment

S lolerclisCmtrol oFosted .

6!o)ooUJoofo'

E.9q)=EocooloaooEd)(DuUJoo)or

nrc. 6. Effect offasting or fasting combined with drug treatment ondaily weight-specific urea excretion. Vertical llnes represent SEM'


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Rr72decrease in the final half of the experiment. Lack ofquantitative recovery of injected urea in the urine (Fig.4) coupled with the above demonstration that plasm"aurea concentration does not increase in response to ipure_a loading implies that, in the ground squirrel, not ailendogenously produced urea may actually be excreted.Therefore, a low level of urea elimination by the squirrel(Fig. 2) does not necessarily correlate wiih a rehuceddegree of protein and amino acid metabolism.

The high metabolic rate and limited fueI reserves ofsmall mammals necessitate rapid adjustment to condi-tions of fasting or water deprivation. fhe capacity of theground squirrel to make these rapid adjustmentsls dem-onstrated by the absence of change in blood urea follow-ing urea loading.The reduced urea elimination discussed above mustelicit either increased storage or induce metabolism ofthe retained urea. Urea hydrolysis in mammals is re-garded as being of bacterial origin (11, 31). There is noevidence in the literature to warrant suspicion of a sep-arate mechanism unique to the ground squirrel. Theresults depicted in Figs. 5 and 6 substantiate this claim.Antibiotic treatment has proven effective in a number of9f1d1es in reducing urea hydrolysis in mamrnals (12,29,32). Drug treatment of fasted squirrels results in a reduc_tion of urea catabolism (Table 2) and leads to enhancedexcretion of urea (Figs. 5 and 6). Colonic or gastric floraare.most likely to be the source of the endogenous ureaseactivity, though the exact site of urea hydrolysis is un-known at present (14, 81).The existence of urea recycling as a nitrogen-conserv-ing mechanisn in rodent hibernitors is unk"nown; nor isit known whether this apparent recycling is operative inS. krteralis d,uring hibernation. Ceitainty the reports ofBenedict and Lee (1) and Galster and Morrlson (13)provide support for such a mechanism operating duringdeep hibernation. They indicate that recoverv oi urea iiREFlIRENCES1. BrNnorcr, F. G., er.ro R. C. Lnr. Hibernation and Marmot phys_lology. Washington, DC: Carnegie Institute, 198g.2. BrNrz, G. L., L. B. Brrrz, ern M. L. Rrronsnl. Respiratoryquotient as an index of seiective tissue catabolism by water depriveilaboratory rats and Spermophilus lateralis. Comp. Biochem. phys_iol. A 38: t2t-127. t971.3. BrNrz, G. L., arvl W. W. MacxrN. The effect of water availabilitvon tissue catabolism during starvation in Richardson's grounisquirreis. Comp. Biochem. physiot-,4. 65: lg1_1g6. 19g0.4. BrNrz, G. L., eNo H. W. Rosnnnnv. Evaporative water loss by.control and starved laboratory rats and Sperm ophilus richardsonii.Comp. Biochem. Physiot. A bg:275-279, lg7g.5. Br,exn, B. H. The effects of kidney structure ancl the annual cvcleon water requirements in golden-mantled grounrl squirrels and- chipmunks. Cctmp. Biochem. physiot. A 58: 418-.4Ig, 1977.6. Bnrccs, M. H. (Editor). Llrea cts a protein Supplement. New york:Pergamon, 1967.7. Cnrr-raN, W. M., eNo D. Tor,r-rrsoN. Blood urea levels and ervth-rocyte fragility to isosmotic urea during hibernation and activiiv ofSpermophilus tridecemlineatus. Comp. Biochem. physiot. A b4:433-435,1976.8. Cour,oMsr, J. J., ervo L. Favnnau. A new simple semi-micromethod for colorimetric determination of urea. Clin. Chem. g: I02_108.1963.9. CurNonr, G. S., E. G. LorrN, D. p. CenrrRoN, A. E. ReNor_o, enoE. B. M,tnr,rss. Hormone-substrate responses to total fasting inlean and obese mice. Am. J. physiot.22g:276-2g8,197b.

STEFFEN, RIGLER, MOORE, AND RIEDESELthe urine following arousals from hibernation is \hth theamount that would be expected on the basis of loss oflean_ body mass. The existence of an operative recyclingmechanism during hibernation is dependent upon bottthe identification of cryoduric microoiganisms capable ofurease activity at low temperatures and the activity ofthe appropriate amino acid-synthesizing enzymur. Thuurea recycling capacity of the hibernator mav be a criticalfactor determining the onset of hibernationl Montova etal. (?0) report a protein-free diet was nearly as effeltiveas starvation in inducing torpor in the garden dormouse.Thus, the nitrogen-sparing effect of urea recycling maypermit some hibernators to delay the onset of hibernationinduced by starvation or protein deficiency.Isotopic studies have demonstrated re-cycling of 15-357o of thgwrea synthesized in the normal human subject(18, 29). The role of urea hydrolysis and nitrogen incor-poration into nonessential amino acids is particularlyimportant in uremic patients maintained on iow proteindiets (32). Recent studies have described the benefit ofsupplementation of low protein diets with ketoacid ana-logues of the essential amino acids (80). Through trans-amination of these analogues, nitrogen released fromurea may be incorporated into essential amino acids. Thepresent study clearly supports the hypothesis that urearecycling in response to nutritional stress is well devel-oped in the golden-mantled ground squirrel.

The authors are indebted to the R. D. Boom family for collectingground squirrels.This research was supported in part by funds from the Univ. of NewMexico Research Allocations Committee and Graduate Student Asso-ciation.Present addresses: G. L. Rigler, 919 Goff Blvd. S.W., Albuquerque,NM 87f 05; A. K. Moore, School of Natural and Mathematical Sciences.Seattle Pacific University, Seattle, WA 981f9._ - Address reprint requests to: M. L. Riedesel, Department of Biology,University of New Mexico, Albuquerque, New Mexico, 87181.Received 24 September 1979; accepted in final form 16 January 19g0.

10. DncucHr, 8., M. Nrryeua, K. Kacora, eNo S. Natrroxa. Role ofintestinal flora on incorporation of,r,N from dietary r5N-urea and'5N-diammonium citrate into tissue proteins in pigs. J. Nutr. .I0g:1572-1579, r978.11. Drlr,uva, A. M., K. Menxr,rv, aNo R. E. Davrns. The absence ofgastric urease in germ-free animals. Biochim. Biophys. Acta lbl:646-650. r968.12. DrNrzrs, R., eNo A. B. HasrrNcs. The effects of antibiotics on ureabreakdown in mice. Proc. Natl. Acad. Sci.39: b71-578, 19b3.13. Gar,smn, W., aNo P. MonnrsoN. Seasonal changes in body com-position of the arctic ground squirrel Can. J. Zool. b4:74-79,1976.14. GrasoN, J. A., N. J. Pam, G. E. Sr,anrx, ar.ro A. M. DawsoN. Therole of the colon in urea metabolism in man. Clin. Sci. Mot. Med..50:51-59, 1976.15. JenrnsoN, E. W., JR., arqo R. A. Mtel. Seasonal changes in bodyfat, water, and basic weight in Citeltus lateralis, Eutamias specio-szs and E. amoenus. J. Mammal.45: 859-865. 1964.16. LESSER, R. W., R. Mov, J. C. Passlront, aro E. W. prurrren.Renal regulation of urea excretion in arousing and homeothermicground squirrels. Comp. Biochem- Physio l. 86: 291-296, 197 0.17. Lr, J. B., J. E. HrccrNi, aro L. S. Jnrransorr,. Changes in proteinturnover in skeletal muscle in response to fasting. Am. J. physiol.236 (Endocrinol. Metab. Gastrointest. Physiol. i): E222-8228,r979.18. LoNc, C. L., M. Jnrverveoeu, amo J. M. KrNNny. Metabolism andrecycling of urea in rnan. Am. J. Clin. Nutr. 3l-. 1J67-1882, 197g.19. Mrllwenn, D. J., P. J. Ganr,rcx, D. O. NNaNyrr-uco. aNn J. C.


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UREA RECYCLING IN ACTIVE GROUND SQUIRRELSWarnnlow. The relative importance of muscle protein synthesisand breakdown in the regulation of muscle mass. Biochem' J 156:185-188,1976.20. MoNrovn, R., L. Antsro, aNo R. Acro. Torpor induced in anyseason by suppression of food proteins in a hibernator, the gardendormouse (Eliomys quercinus). Comp. Biochem. Physiol' A 62:371-376. t979.21. MoY, R. M. Renal function in the hibernating ground squirrel'Spermophilus c olumbianus. Am. J' Phy sio l. 220: 7 47 -7 53' 197 l'22. Mnosovsxv, N. Lipid programmes and life strategies in hiberna-tors. Arn. Zool. 16:685-697, 1976.

23. Nnr,soN, R. A. Urea metabolism in the hibernating black bear'Kidney Int. Suppl.8: 5177-5179, 1978.24. NusoN, R. A., J. D. JoNns, H. W. WanNrR, D. B. McGIll, aNoC. F. Coon. Nitrogen metabolism in bears: urea metabolism insummer staruation and in winter sleep and the role of the urinarybladder in water and nitrogen conservation. Mayo Clin' Proc' 50:141-146.1975.25. NusoN, R. A., H. W. WenNnn, J. D. JoNns, R. D. Et-lrrso*, eNoP. E. ZollueN. Metabolism of bears before, during and after wintersleep. Az. J. Physiol.224:491-496' 1973.

R17326. Passuonn, J. C., E. W. Ppzrrrun, AND J. R. Trupr'troN' Ureaexcretion in the hibernating columbian ground squirrel (Spermo-philus columbianus\. J. Exp. Zool 192: 83-86, 1975'27. hnconczr, E., L. InoNs, A. Ko.r, AND A. S. MecFnRr-axn' Isotopicstudies of urea metabolism in rabbits. Biochem. J 95: 521-535'

1965.28. Ttupnl, G. E., X. J. Muslccnrn, ersn S. B. JoNns. Mechanismsresponsi6le for decreased glomerular filtration in hibernation andhypothermia. J. Appt. Physiol.: Respirat. Enuiron' Exercise Phys'iol. 42: 420-425,1977.29. War,snn, M., eNo L. J. BonnNr,os. Urea metabolism in man' JClin. Inuest.38: 1617-1626, 1959.30. Walsnn, M., W. E. MrrcH, aNn V. U. Colr-Irn The effect ofnutritional therapy on the course of chronic renal failure C/in'Nephrol ll: 66-70, 1979'31. WnoNc, O. Nitrogen metabolism in the gut' Am' J' Clin' Nufr' 31:1587-1593, 1978.32. WnoNc, O., B. J. HoucnroN, P. Rrcnenos, aNo D R' WILSoN'The fate oi intestinai urea in normal subjects and patients withuremia. In: lJrea and the Kidney' edited by B' Schmidt-Nielsen'Amsterdam: Excerpta Medica, 1970, p. 461-469'

Urea recyclittg in active golden-mantled ground squirrels

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