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 ~