11.9 Neurotransmitters

11.9 Neurotransmitters • Language of nervous system • 50 or more neurotransmitters have been identified • Most neurons make two or more neurotransmitters – Neurons can exert several influences • Usually released at different stimulation frequencies • Classified by: – Chemical structure – Function Classification of Neurotransmitters by Chemical Structure (1 of 12) • Acetylcholine (ACh) – First identified and best understood – Released at neuromuscular junctions  Also used by many ANS neurons and some CNS neurons – Synthesized from acetic acid and choline by enzyme choline acetyltransferase – Degraded by enzyme acetylcholinesterase (AChE) Classification of Neurotransmitters by Chemical Structure (2 of 12) • Biogenic amines – Catecholamines  Dopamine, norepinephrine (NE), and epinephrine: made from the amino acid tyrosine – Indolamines  Serotonin: made from the amino acid tryptophan  Histamine: made from the amino acid histidine – All widely used in brain: play roles in emotional behaviors and biological clock – Used by some ANS motor neurons  Especially NE – Imbalances are associated with mental illness Classification of Neurotransmitters by Chemical Structure (3 of 12) • Amino acids – Amino acids make up all proteins: therefore, it is difficult to prove which are neurotransmitters – Amino acids that are proven neurotransmitters  Glutamate  Aspartate   Glycine  GABA: gamma ( )-aminobutyric acid Classification of Neurotransmitters by Chemical Structure (4 of 12) • Peptides (neuropeptides) – Strings of amino acids that have diverse functions  Substance P – Mediator of pain signals  Endorphins – Beta endorphin, dynorphin, and enkephalins: act as natural opiates; reduce pain perception  Gut-brain peptides – Somatostatin and cholecystokinin play a role in regulating digestion Classification of Neurotransmitters by Chemical Structure (5 of 12) • Purines – Monomers of nucleic acids that have an effect in both CNS and PNS  ATP, the energy molecule, is now considered a neurotransmitter  Adenosine is a potent inhibitor in brain – Caffeine blocks adenosine receptors  Can induce Ca2+ influx in astrocytes Classification of Neurotransmitters by Chemical Structure (6 of 12) • Gases and lipids – Gasotransmitters  Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide gases (H2S)  Bind with G protein–coupled receptors in brain  Lipid soluble and are synthesized on demand  NO involved in learning and formation of new memories, as well as brain damage in stroke patients, and smooth muscle relaxation in intestine  H2S acts directly on ion channels to alter function Classification of Neurotransmitters by Chemical Structure (7 of 12) – Endocannabinoids  Act at same receptors as THC (active ingredient in marijuana)  Most common G protein–linked receptors in brain  Lipid soluble  Synthesized on demand  Believed to be involved in learning and memory  May be involved in neuronal development, controlling appetite, and suppressing nausea Classification of Neurotransmitters by Chemical Structure (8 of 12) • Neurotransmitters exhibit a great diversity of functions • Functions can be grouped into two classifications: – Effects – Actions Classification of Neurotransmitters by Chemical Structure (9 of 12) • Effects: excitatory versus inhibitory – Neurotransmitter effects can be excitatory (depolarizing) and/or inhibitory (hyperpolarizing) – Effect determined by receptor to which it binds  GABA and glycine are usually inhibitory  Glutamate is usually excitatory  Acetylcholine and NE bind to at least two receptor types with opposite effects – ACh is excitatory at neuromuscular junctions in skeletal muscle – ACh is inhibitory in cardiac muscle Classification of Neurotransmitters by Chemical Structure (10 of 12) • Actions: direct versus indirect – Direct action: neurotransmitter binds directly to and opens ion channels  Promotes rapid responses by altering membrane potential  Examples: ACh and amino acids – Indirect action: neurotransmitter acts through intracellular second messengers, usually G protein pathways  Broader, longer-lasting effects similar to hormones  Biogenic amines, neuropeptides, and dissolved gases Classification of Neurotransmitters by Chemical Structure (11 of 12) • Actions: direct versus indirect (cont.) – Neuromodulator: chemical messenger released by neuron that does not directly cause EPSPs or IPSPs but instead affects the strength of synaptic transmission  May influence synthesis, release, degradation, or reuptake of neurotransmitter  May alter sensitivity of the postsynaptic membrane to neurotransmitter.  May be released as a paracrine – Effect is only local Classification of Neurotransmitters by Chemical Structure (12 of 12) • Channel-linked receptors – Ligand-gated ion channels – Action is immediate and brief – Excitatory receptors are channels for small cations  Na+ influx contributes most to depolarization – Inhibitory receptors allow Cl– influx that causes hyperpolarization Channel-Linked Receptors Cause Rapid Synaptic Transmission Figure 11.16 Channel-linked receptors cause rapid synaptic transmission. Neurotransmitter Receptors (1 of 2) • G protein–linked receptors – Responses are indirect, complex, slow, and often prolonged – Involves transmembrane protein complexes – Cause widespread metabolic changes – Examples:  Muscarinic ACh receptors  Receptors that bind biogenic amines  Receptors that bind neuropeptides Neurotransmitter Receptors (2 of 2) • G protein–linked receptors (cont.) – Mechanism:  Neurotransmitter binds to G protein–linked receptor, activating G protein  Activated G protein controls production of second messengers, such as cyclic AMP, cyclic GMP, diacylglycerol, or Ca2+  Second messengers can then: – Open or close ion channels – Activate kinase enzymes – Phosphorylate channel proteins – Activate genes and induce protein synthesis G Protein–Coupled Receptors Cause the Formation of Intracellular Second Messengers (1 of 7) Figure 11.17 G protein–coupled receptors cause the formation of intracellular second messengers. G Protein–Coupled Receptors Cause the Formation of Intracellular Second Messengers (2 of 7) Figure 11.17 G protein–coupled receptors cause the formation of intracellular second messengers. G Protein–Coupled Receptors Cause the Formation of Intracellular Second Messengers (3 of 7) Figure 11.17 G protein–coupled receptors cause the formation of intracellular second messengers. G Protein–Coupled Receptors Cause the Formation of Intracellular Second Messengers (4 of 7) Figure 11.17 G protein–coupled receptors cause the formation of intracellular second messengers. G Protein–Coupled Receptors Cause the Formation of Intracellular Second Messengers (5 of 7) Figure 11.17 G protein–coupled receptors cause the formation of intracellular second messengers. G Protein–Coupled Receptors Cause the Formation of Intracellular Second Messengers (6 of 7) Figure 11.17 G protein–coupled receptors cause the formation of intracellular second messengers. G Protein–Coupled Receptors Cause the Formation of Intracellular Second Messengers (7 of 7) Figure 11.17 G protein–coupled receptors cause the formation of intracellular second messengers.