Mixed nicotinic and muscarinic features of cholinergic receptor coupled to secretion in bovine chromaffin cells

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.11.4860· OSTI ID:6096979

Shirvan, M H; Pollard, H B; Heldman, E ^[1]

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1. National Inst. of Health, Bethesda, MD (United States)

Acetylcholine evokes release from cultured bovine chromaffin cells by a mechanism that is believed to be classically nicotinic. However, the authors found that the full muscarinic agonist oxotremorine-M (Oxo-M) induced a robust catecholamine (CA) secretion. By contrast, muscarine, pilocarpine, bethanechol, and McN-A-343 did not elicit any secretory response. Desensitization of the response to nicotine by Oxo-M and desensitization of the response to Oxo-M by nicotine suggest that both nicotine and Oxo-M were acting at the same receptor. Additional experiments supporting this conclusion show that nicotine-induced secretion and Oxo-M-induced secretion were similarly blocked by various muscarinic and nicotinic antagonists. Moreover, secretion induced by nicotine and Oxo-M were Ca{sup 2+} dependent, and both agonists induced {sup 45}Ca{sup 2+} uptake. Equilibrium binding studies showed that ({sup 3}H)Oxo-M bound to chromaffin cell membranes with a K{sub d} value of 3.08 {times} 10{sup {minus}8}M and a Hill coefficient of 1.00, suggesting one binding site for this ligand. Nicotine inhibited Oxo-M binding in a noncompetitive manner, suggesting that both ligands bind at two different sites on the same receptor. They propose that the receptor on bovine chromaffin cells that is coupled to secretion represents an unusual cholinergic receptor that has both nicotinic and muscarinic features.

• OSTI ID: 6096979
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:11; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETYLCHOLINE
ADRENAL GLANDS
ALKALINE EARTH ISOTOPES
ALKALOIDS
AMINES
AMMONIUM COMPOUNDS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CALCIUM 45
CALCIUM ISOTOPES
CATECHOLAMINES
DAYS LIVING RADIOISOTOPES
DRUGS
ENDOCRINE GLANDS
ESTERS
EVEN-ODD NUCLEI
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPES
KINETICS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
NEUROREGULATORS
NICOTINE
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PHENOLS
POLYPHENOLS
PROTEINS
PYRIDINES
PYRROLES
PYRROLIDINES
QUATERNARY COMPOUNDS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SECRETION
UPTAKE