NRSC 2100 1st Edition Lecture 9 Neurotransmitters The Messengers Criteria for neurotransmitter status 1 Must be found in presynaptic terminal neuron 2 Enzymes for synthesis 3 Released from presynpatic terminals 4 Action on postsynaptic neuron i e PSP etc 5 Postsynaptic receptors protein receptors 6 Deactivation Reuptake or degradation 7 Predictable pharmacological action Major classes of neurotransmitters I Small neurotransmitter molecules A Amino acids 1 Excitatory amino acids Glutamate Aspartate Enzyme glutamic acid decarboxylase GAD transforms glutamate into GABA VGAT vesicular GABA transporter fills vesicles Membrane GABA transporters Mostly responsible for fast IPSPs 30 40 of CNS neurons utilize GABA I Small neurotransmitter molecules A Amino acids 2 Inhibitory amino acids b Glycine Enzyme glutamic acid decarboxylase GAD transforms glutamate into GABA VGAT vesicular GABA transporter fills vesicles Membrane GABA transporters Mostly responsible for fast IPSPs 30 40 of CNS neurons utilize GABA 1 I Small neurotransmitter molecules A Amino acids 2 Inhibitory amino acids b Glycine Derived mostly from conversion of serine with enzyme serine hydroxymethyltransferase Concentrated in vesicles by vesicular inhibitory amino acid transporter VIAAT Membrane Glycine transporters Mostly responsible for fast IPSPs especially in spinal cord interneurons I Small neurotransmitter molecules B Amines 1 Acetylcholine Ach Found in PNS and CNS PNS neuromuscular junctions autonomic nervous system I Small neurotransmitter molecules B Amines 2 Catecholamines a Dopamine b Norepinephrine Epinephrine a Dopamine movement attention learning reward degeneration of Substantia Nigra in midbrain Parkinson s disease loss of DA schizophrenia too much DA b Norepinephrine and Epinephrine released by SNS and adrenals control alertness wakefulness alarm Vesicular transporters concentrate all catecholamines in vesicles and this system includes metabolic enzymes MAOs and membrane transporters for inactivation I Small neurotransmitter molecules B Amines 3 Indolamine a Serotonin regulates mood emotional behavior sleep and arousal target system of some hallucinogenic LSD and antidepressant drugs SSRIs I Small neurotransmitter molecules C Purine ATP often packaged in synaptic vesicles with other neurotransmitters e g DA and is co released during neurotransmission A2a receptors targets of caffeine s effects D Histamine believed to be widely employed in the central nervous system clearest role in sleep wake functions as evidenced by effects of antihistamines many cold medicines contain H1 receptor antagonists 2 II Large neurotransmitter molecules Peptides Neuropeptides relatively small amino acid chains Mostly synthesized in neural cell bodies packaged within Golgi apparatus trans Golgi transported to synaptic terminals and broken down by various peptidases Wide variety and functions ex endorphins endogenous opiates pain cholecystokinin gut peptide food intake vasopressin fluid regulation III Retrograde messengers A Endocannabinoids Synthesized in post synaptic elements de novo no vesicular storage upon secondmessenger stimulation Ca etc Anandamine and 2 arachidonylglycerol 2 AG easily cross bilayer membranes and interact with pre synaptic cannabinoid CB1 receptors Widespread inhibitory functions in CNS III Retrograde messengers B Soluble gases Nitric oxideAlso synthesized in post synaptic elements de novo no vesicular storage upon second messenger Ca etc stimulation of nitric oxide synthase NOS NO easily crosses bilayer membranes and interact with pre synaptic soluble enzyme guanylyl cyclase sGC cGMP Widespread relaxing effects in vasculature What is Dale s principle The hypothesis that a neuron releases the same neurotransmitter at all its synapses However many neurons synthesize and release multiple neurotransmitters at their synapses 3