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 ~

ACh A Botulinum toxin BWSV curare atropine AChE AChE N M

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 ~

Monoamines MAO Reserpine A COMT MAO

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 NEa & NEb ~

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 ~