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Direct Mechanisms via Ligand-Direct Mechanisms via Ligand-gated Channel: gated Channel: Nicotinic ACh Nicotinic ACh receptorreceptor
Change in ion permeability changes membrane potential
Signal Transductio
n Activated receptor
alters intracellular molecules to create response
First messenger transducer amplifier second messenger
Fig 6-8
Most Signal Transduction uses Most Signal Transduction uses G-Protein G-Protein
Hundreds of types known
Bind GDP / GTP (name!)
Activated G proteins 1. Open ion channels 2. Alter intracellular enzyme activity, e.g.: via adenyl
cyclase (amplifier) cAMP (2nd messenger) protein kinase activation phosphorylated protein
G-Protein is a membrane-associated protein that binds to GDP
G - Protein mediated Signal Transduction
Muscarinic ACh receptor
Epinephrine Signal Transduction
Compare to fig 6-11
Other signal MoleculesOther signal Molecules Not all are proteins Ca2+ is a common cytosolic messenger NO (nitric oxide) is a neurotransmitter Lipids:
Leukotrienes cause contraction of bronchiolar smooth muscle
Prostanoids have several communicative roles, e.g., inflammation
Modulation of Signal Pathways
Receptors exhibit
Saturation, yetReceptors can be up- or down-regulated (e.g. drug tolerance)
Specificity, yet- Multiple ligands for one receptor: Agonists (e.g. nicotine) vs. antagonists (e.g. tamoxifen)- Multiple receptors for one ligand (see Fig 6-18)
Competition
Aberrations in signal transduction causes many diseases (table 6-3)
Many drugs target signal transduction pathway (SERMs, -blockers etc.)
In Summary: In Summary: Receptors Explain WhyReceptors Explain Why
Chemicals traveling in bloodstream act only on specific tissues
One chemical can have different effects in different tissues
Homeostasis and Homeostasis and “Homeodynamics”“Homeodynamics”
Cannon's Postulates (concepts) of properties of homeostatic control systems
1. Nervous regulation of internal environment
2. Tonic level of activity
3. Antagonistic controls (insulin/glucagon)
4. Chemical signals can have different effects on different tissues
Failure of homeostasis?
Fig 6-19
Tonic Control
Control Pathways: Response and Feedback
LoopsMaintain homeostasisMaintain homeostasis
Local – paracrines and Local – paracrines and autocrinesautocrines
ThresholdThreshold (= minimum stimulus (= minimum stimulus necessary to initiate signal)necessary to initiate signal)
Fig 6-23
Afferent PathwayAfferent Pathway
From receptor to From receptor to integrating center integrating center
Afferent pathways of Afferent pathways of nervous system: ?nervous system: ?
Endocrine system has no Endocrine system has no afferent pathwayafferent pathway (stimulus comes directly (stimulus comes directly into endocrine cell)into endocrine cell)
Integrating CenterIntegrating Center
Neural reflexes usually in the CNS; endocrine integration in the endocrine cell itself
Receives info about change
Interprets multiple inputs and compares them with set-point
Determines appropriate response (→ alternative name: control center)
Efferent PathwayEfferent Pathway
From integrating From integrating center to effectorcenter to effector
NS NS electrical and electrical and chemical signalschemical signals
ES ES chemical signals chemical signals (hormones)(hormones)
EffectorsEffectors
Cells or tissues carrying out response
Target for NS:muscles and glands and some adipose
tissues
Target for ES:any cell with proper receptor
Responses Responses at 2 levels:at 2 levels:
1.1. Cellular response of target cell Cellular response of target cell opening of a channel Modification of an enzyme etc...
2.2. Systemic response at Systemic response at organismal levelorganismal level
vasodilation, vasoconstriction Lowering of blood pressure etc....
Feedback Loops Modulate the Response
Loop Response loop is only half of reflex!
Response becomes part of stimulus and feeds back into system.
Purpose: keep system near a set point
2 types of feedback loops:- feedback loops+ feedback loops
Fig 6-25
Fig 6-26
The Body’s 2 Control The Body’s 2 Control SystemsSystems
Variation in speed, specificity and duration of action
The two systems allow for 4 different types of biological reflexes