~BN13 neurotransmitters.ppt

Neurotransmitters

Lecture 13

CRITERIA

NT found in axon terminals NT released by action potentials Synthesis identified External application mimic normal

Response Pharmacology same for normal and

externally applied NT ~

Lock & Key Model

NT binds to receptor

NT = key

Receptor = lock Receptor changes shape

determines if EPSP or IPSP

receptor subtypes NOT NT ~

Structure-activity relationship

NT fits receptor site key & lock

Change structure of drug... change its affinity

increase or decrease may bind to different receptor

Behavior mediated by synaptic activity most drugs act at synapse ~

Acetylcholine - ACh

Most abundant NT in Peripheral N.S. also found in Central N.S. Precursor = choline

Degraded by acetylcholinesterase- AChE

Nicotinic receptor – ionotropic *Nonselective ionophores *Requires 2 Ach for activation

Muscarinic receptor - metabotropic ~

ACh - Distribution

Peripheral N.S. Excites somatic muscle Autonomic NS

Ganglia Parasympathetic NS Neuroeffector junction

Central N.S. - widespread Hippocampus Hypothalamus ~

Excitatory Amino Acids: Glutamate

Primary NT in CNS excitatory neurons Nonessential amino acids

Synthesis Precursor glutamine from astroglia

Termination presynaptic & glial reuptake ~

Excitatory Amino Acids: Glutamate

Receptor subtypes Metabotropic (mGlu-R)

Inhibition of Na+ & Ca++ channels Ionotropic: NMDA-R; AMPA-R

nonselective Excitotoxicity

Following brain injury Elevated Glu activity

Aspartate ~

Inhibitory Amino Acids: Glycine

Primarily spinal cord Cl- channels Strychnine is antagonist ~

Inhibitory Amino Acids: GABA

Gamma-aminobutyric acid - GABAergic

Major NT in brain inhibitory systems Receptor subtypes

GABAA / GABAC ionotropic Cl- channel

GABAB - metabotropic K+ channels Precursor = glutamate ~

Biogenic Amines (Monamines)

Amino acid precursors single amine group

2 groups Catecholamines - catechol ring

Tyrosine precursor Indolamine - indole ring

Tryptophan precursor Affected by many of same drugs ~

Monamines

Catecholamines

Dopamine - DA Dopaminergic

Norepinephrine - NE Noradrenergic

Epinephrine - E Adrenergic

Indolamines

Serotonin - 5-HT

Serotonergic

Monamines

Terminated by... reuptake monoamine oxidase - MAO catechol-O-methyltranferase - COMT also in liver

Reserpine leaky vesicles depletes monoamines ~

Dopamine

Only in central nervous system mostly inhibitory systems

Reward Schizophrenia Movement

Nigrostriatal Pathway At least 5 DA-R types: D1, D2, etc. ~

Norepinephrine

Peripheral N.S. Sympathetic neuroeffector junction Adrenal glands

Central N.S. Hypothalamus Locus coeruleus

Alpha & Beta receptor subtypes NE & NE ~

Serotonin

NOT a catecholamine Peripheral

98% in blood & smooth muscle Central N.S.

Raphe nucleus Hypothalamus

R subtypes: 5HT1 & 5HT2 ~

Neuropeptide

Chains of amino acids Synthesis in soma

Often neuromodulators alters sensitivity of neurons slower, longer-lasting effects

Substance P - pain signaling Endorphins - analgesia, euphoria ~

Endorphins

Opioids Dynorphin met-enkephalin leu-enkephalin Beta-endorphin

Receptor subtypes: mu1, mu2, kappa, delta ~

Unconventional NTs

Retrograde messengers Ca++-dependent Not stored in vesicles

Nitric Oxide - It’s a gas Synthesis on demand by NO

synthase LTP ~

Unconventional NTs

Endocannabinoids Anandamide 2 - AG Inhibits presynaptic GABA release Synthesis by enzymatic

degradation of membrane ~