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Distribution and function of muscarinic receptor subtypes in the ovine submandibular gland.

Journal article
Authors Gunnar Tobin
Anders Ryberg
S Gentle
A V Edwards
Published in Journal of applied physiology (Bethesda, Md. : 1985)
Volume 100
Issue 4
Pages 1215-23
ISSN 8750-7587
Publication year 2006
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 1215-23
Language en
Links dx.doi.org/10.1152/japplphysiol.007...
Keywords Animals, Atropine, pharmacology, Chorda Tympani Nerve, physiology, Electric Stimulation, Female, Immunohistochemistry, Muscarinic Antagonists, pharmacology, Piperidines, pharmacology, Pirenzepine, pharmacology, Receptor, Muscarinic M1, analysis, antagonists & inhibitors, metabolism, Receptor, Muscarinic M4, analysis, antagonists & inhibitors, metabolism, Receptor, Muscarinic M5, analysis, antagonists & inhibitors, metabolism, Salivation, drug effects, Sheep, Submandibular Gland, blood supply, innervation, metabolism, Time Factors, Vasodilation, drug effects
Subject categories Pharmacology and Toxicology, Pharmacology, Physiology

Abstract

The effects of muscarinic receptor antagonists on responses to electrical stimulation of the chorda-lingual nerve were determined in pentobarbitone-anesthetized sheep and correlated to the morphology of tissue specimens. Stimulation at 2 Hz continuously, or in bursts of 1 s at 20 Hz every 10 s, for 10 min induced similar submandibular fluid responses (19 +/- 3 vs. 21 +/- 3 microl x min(-1) x g gland(-1)), whereas vasodilatation was greater during stimulation in bursts (-52 +/- 4 vs. -43 +/- 5%; P < 0.01). Continuous stimulation at 8 Hz induced substantially greater responses (66 +/- 9 microl x min(-1) x g gland(-1) and -77 +/- 3%). While atropine (0.5 mg/kg iv) abolished the secretory response at 2 and 20 Hz (1:10 s), a small response persisted at 8 Hz (<5%). The "M1-selective" antagonist pirenzepine (40 microg/kg iv) reduced the fluid response at all frequencies tested (P < 0.05-0.01), most conspicuously at 2 Hz (reduced by 69%). Methoctramine ("M2/M4-selective"; 100 microg/kg iv; n = 5) had no effect on fluid or the vascular responses but increased the protein output at 2 (+90%, P < 0.05) and 8 Hz (+45%, P < 0.05). The immunoblotting showed distinct bands for muscarinic M1, M3, M4, and M5 receptors, and immunohistochemistry showed muscarinic M1 and M3 receptors to occur in the parenchyma. Thus muscarinic M1 receptors contribute to the secretory response to parasympathetic stimulation but have little effect on the vasodilatation in the ovine submandibular gland. Increased transmitter release caused by blockade of neuronal inhibitory receptors of the M4 subtype would explain the increase in protein output.

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