I. Small neurotransmitter molecules:A. Amino acids:1. Excitatory amino acids:GlutamateAspartateEnzyme glutamic acid decarboxylase (GAD) transforms glutamate into GABA;VGAT (vesicular GABA transporter) fills vesicles;Membrane GABA transporters;Mostly responsible for fast IPSPs30-40% of CNS neurons utilize GABAI. Small neurotransmitter molecules:A. Amino acids:2. Inhibitory amino acids:b. GlycineEnzyme glutamic acid decarboxylase (GAD) transforms glutamate into GABA;VGAT (vesicular GABA transporter) fills vesicles;Membrane GABA transporters;Mostly responsible for fast IPSPs30-40% of CNS neurons utilize GABAI. Small neurotransmitter molecules:A. Amino acids:2. Inhibitory amino acids:b. GlycineDerived 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 interneuronsI. Small neurotransmitter molecules:B. Amines:1. Acetylcholine (Ach)*Found in PNS and CNS-PNS: - neuromuscular junctions- autonomic nervous systemI. Small neurotransmitter molecules:B. Amines:2. Catecholaminesa. Dopamineb. Norepinephrine, Epinephrinea. Dopamine- movement, attention, learning, reward- degeneration of Substantia Nigra inmidbrain = Parkinson’s disease (loss of DA)- schizophrenia (too much DA)b. Norepinephrine and Epinephrine- released by SNS and adrenals- control alertness/wakefulness; alarmVesicular 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. Indolaminea. 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).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 second-messenger 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 andrelease multiple neurotransmitters at their synapses.NRSC 2100 1st EditionLecture 9Neurotransmitters: The Messengers!Criteria for neurotransmitter status:1. Must be found in presynaptic terminal/neuron2. Enzymes for synthesis3. Released from presynpatic terminals4. Action on postsynaptic neuron (i.e., PSP, etc.)5. Postsynaptic receptors (protein receptors)6. Deactivation - Reuptake or degradation7. 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 GABAI. 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 GABA1I. 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 interneuronsI. Small neurotransmitter molecules:B. Amines:1. Acetylcholine (Ach)*Found in PNS and CNS-PNS: - neuromuscular junctions - autonomic nervous systemI. Small neurotransmitter molecules:B. Amines:2. Catecholaminesa. Dopamineb. Norepinephrine, Epinephrinea. Dopamine - movement, attention, learning, reward - degeneration of Substantia Nigra inmidbrain = 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. Indolaminea. 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