Mechanisms of facilitation and muscarinic or alpha-adrenergic inhibition of acetylcholine and noradrenaline secretion from peripheral nerves. 1982

P Alberts
Department of Physiology I, Karolinska Institutet, Stockholm, Sweden.

The muscarinic acetylcholine (ACh) receptor from rat brain has been partially purified and characterized. The molecular weight of the smallest subunit of the receptor protein obtained by a chaotropic agent is 30,000 dalton, while the protein found in sodium dodecyl sulphate polyacrylamide gels has a molecular weight of 80,000 dalton. The isoelectric point is in the range 4.5 to 5.1. The low affinity dissociation constant for agonists of the alpha-adrenoceptor from rat and guinea-pig brain, and of the muscarinic ACh receptor from guinea-pig ileum longitudinal muscle-myenteric plexus preparation, is increased 2-3-fold at potassium concentrations of 80-100 mM. The transmitter stores of noradrenergic nerves of guinea-pig vas deferens were labelled by preincubation with 3H-noradrenaline (3H-NA), and those of cholinergic nerves of guinea-pig ileum myenteric plexus were labelled by preincubation with 3H-choline. The mechanisms underlying frequency dependent facilitation and presynaptic receptor mediated depression of transmitter secretion were studied. The secretion evoked by electrical stimulation required both invasion of the nerve terminals and activation of the depolarization-secretion coupling in varicosities, while that evoked by high potassium (40-110 mM) was due to direct depolarization varicosities. Blockade of presynaptic alpha-adrenergic and muscarinic autoreceptors by phentolamine and atropine, respectively, caused 4-5-fold greater increase in the secretion of labelled transmitter evoked by electrical than by potassium stimulation from noradrenergic and cholinergic terminals. This suggests that depression of transmitter secretion is exerted mainly by control of the invasion of nerve terminals, and only to a minor extent by control of depolarization-secretion coupling in invaded terminals. Autoinhibition of transmitter secretion involves regulation of calcium availability and is antagonized by facilitation. Endogenous cyclic nucleotides are not critically involved in either facilitation, or alpha-adrenergic or muscarinic autoreceptor mediated control of transmitter secretion in these nerves.

UI MeSH Term Description Entries
D007082 Ileum The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
D007526 Isoelectric Point The pH in solutions of proteins and related compounds at which the dipolar ions are at a maximum. Isoelectric Points,Point, Isoelectric,Points, Isoelectric
D008297 Male Males
D008970 Molecular Weight The sum of the weight of all the atoms in a molecule. Molecular Weights,Weight, Molecular,Weights, Molecular
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D009411 Nerve Endings Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS. Ending, Nerve,Endings, Nerve,Nerve Ending
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010277 Parasympathomimetics Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here. Parasympathomimetic Agents,Parasympathomimetic Drugs,Parasympathomimetic Effect,Parasympathomimetic Effects,Agents, Parasympathomimetic,Drugs, Parasympathomimetic,Effect, Parasympathomimetic,Effects, Parasympathomimetic
D010525 Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Endoneurium,Epineurium,Perineurium,Endoneuriums,Epineuriums,Nerve, Peripheral,Nerves, Peripheral,Perineuriums,Peripheral Nerve

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