5-hydroxyindoleacetic acid (5-HIAA) metabolic disposition of 5-HT
lysergic acid N(C2Hs)2
r' h ergometrine NHCH(CH3)CH20H H
methysergideNHCH(CH3)CH2OH ch3 y amine ergot alkaloids
Cholinergic neuron systems occur in the peripheral and central nervous systems. In the CNS, they are widespread, and release ACh opposite muscarinic (M) and ni-cotinic (N) receptors. M receptors outnumber N receptors 10-100-fold in the CNS. In the CNS, major cholinergic pathways originate from cell bodies in the septum, diagonal band of Broca, and basal nucleus in the ventral forebrain, and project to the hippocampus, interpeduncu-lar nuclei, and neocortex, respectively. Cortical cholinergic innervation appears to play a role in memory, and may be involved in the etiology of Alzheimer's disease (see p. 376). Within the striatum there are smaller cholinergic neurons involved in control of fine movement; blockade of these muscarinic receptors with atropine, a muscarinic antagonist, can be used to treat parkinsonian tremor. There are cholinergic cell bodies in the brain stem tegmentum, and these project to hypothalamus and thalamus. Choliner-gic cell bodies of the cranial parasympa-thetic outflow occur in the brain stem, and lower down in the spinal cord in the sacral region. In the spinal cord are also the cholinergic cell bodies of the thoraco-lumbar preganglionic sympathetic outflow and those of the a-motoneurons.
The term muscarinic is derived from the poisonous mushroom Amanita muscaria, which contains muscarine. Muscarine produces parasympathomimetic effects after injection. A number of different subtypes of muscarinic receptors have been discovered, encoded by distinct but homologous genes. These receptors have been termed M1-M5, and different types are found in different proportions in different tissues. Despite their different genetic origin, the subtypes display remarkably similar patterns of affinity for various agonists and antagonists, and some, such as zamifenacin, an M3 recep tor antagonist, are being evaluated, for example, treatment of irritable bowel syndrome. The receptors transduce their lig-and-activated signal through coupling to guanine nucleotide-binding regulatory proteins (G proteins).
There is evidence that in smooth muscle the balance between the contracted or relaxed state may depend on the relative activity of the sympathetic or par-asympathetic drive to the muscle. The sympathetic drive to smooth muscle, mediated by the neurotransmitter norepi-nephrine, activates a Gs protein, which activates the enzyme adenylate cyclase. This results in increased cAMP production, and relaxation of the muscle. ACh is released by the parasympathetic nerve terminal and acts on M2 receptors, which activate an inhibitory Gi protein, which in turn moves to and inactivates adenylate cyclase. Thus, synthesis of the second messenger cAMP is inhibited, and this increases muscle contractility. Also, ACh binds to an M3 receptor, which activates a Gq protein, which activates the enzyme phospholipase C (PLC), which in turn activates the IP3 second messenger system, which results in Ca2+ mobilization and increased contractility. A similar balance between noradrenergic and muscarinic inputs to neurons and glia may operate in the CNS.
Muscarinic receptors occur presynap-tically as well as postsynaptically on CNS
neurons, and the presynaptic receptors function as autoreceptors that, when activated by the released neurotransmitter, namely acetylcholine, modulate release of ACh. Both nicotinic and muscarinic receptors may occur at the same synapse. Recently, nicotinic autoreceptors have been found presynaptically in the substantia nigra, striatum, medial septum, hippocampus, and medial habenula, and may occur in other brain areas as well.
¡triatum septal nuclei.
diagonal band, of Broca hippocampus.
spinal cord: preganglionic/ parasympathetic a-motoneuron outflow cholinergic pathways in the CNS
¡triatum septal nuclei.
diagonal band, of Broca
hypothalamus cerebellum brain stem tegmentum brain stem parasympathetic outflow hypothalamus cerebellum brain stem tegmentum brain stem parasympathetic outflow selective antagonists receptor subtypes pirenzepine himbacine zamifenacin himbacine nicotininc autoreceotor
Mi cerebral cortex
M3 salivary gland; GIT
M4 rabbit lung; rat GIT M5
guinea pig ileum
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.