Neurotransmitters & Receptors Lecture 10

Ligands & Receptors n Ligand l Neurotransmitters (NT) & Drugs n Receptor proteins l Control ion channels n NT binds to receptor l Activation l EPSP or IPSP l Receptor subtypes ~

Lock & Key Model n NT binds to receptor l NT = key l Receptor = lock n Affinity (attraction) l Binding site l Physical fit l Electrical fit ~

Receptor B Receptor A n Same NT can bind to different -R l different part of NT ~ NT

Receptor Subtypes n Same NT l Binds to many receptor subtypes l Produce different effects l EPSP or IPSP n All NT systems l Several subtypes each l Drug side effects ~

Ionotropic receptors n Ligand-gated channels l Ion channels n NT directly controls channel l fast action l transient ~

Metabotropic receptors n Requires energy l GTP n Receptor indirectly controls channel l G protein-gated ion channels l 2d messenger systems n neuromodulation l slower action l changes in sensitivity of neuron ~

2d Messenger Systems n Effects relatively slow n Signal amplification l 1 NE  activate adenlyl cyclase  l ATP  1000s cAMP  10,000s  l cAMP  10,000s phosphates n Effects l Control channel l Alter properties of receptors l regulation of gene expression ~

G protein: Protein Phosphorylation R ACAC PKA G GTP ATP cAMP P

G protein: Protein Phosphorylation R ACAC PKA G GTP ATP cAMP P Pore

Neurotransmitters n Chemical messengers l Signal between cells n Acetylcholine (ACh) n Monoamines n Amino Acids n Peptides n Purines & Gases ~

Acetylcholine - ACh n Peripheral N.S. l Skeletal muscle contraction n Autonomic NS l Ganglia l Parasympathetic neuroeffector junction n Central N.S. - widespread l Hippocampus l Hypothalamus ~

Acetylcholine - ACh n Receptor subtypes: 2 major groups n Nicotinic receptors - ionotropic l excitatory n Muscarinic receptors - metabotropic l excitatory or inhibitory n Degraded by acetylcholinesterase- l AChE ~

Monoamines n 2 groups l Amino acid precursors l Catecholamines - tyrosine l Indolamine - tryptophan n Affected by many of same drugs ~

Monoamines n Catecholamines l Dopamine - DA u Dopaminergic l Norepinephrine - NE u Noradrenergic l Epinephrine - E u Adrenergic ~ n Indolamines l Serotonin - 5HT u Serotonergic

Monoamines n Terminated by... l reuptake l MAO - monoamine oxidase l COMT - catechol-O-methyltransferase l also in liver n Reserpine  blocks storage l initially stimulates NT release l profound depletion over several days ~

Amino Acids n GABA l Gamma-amino-butyric acid l Inhibitory l CNS n Glutamate l Excitatory l CNS ~

Other Neurotransmitters n Peptides l Amino acid chains l Substance P l Endorphins n Purines l ATP n Nitric Oxide (NO) l Poisonous gas? l Carbon monoxide? n Anandamide l At THC receptors n Many others ~