Muscarinic receptor modulation of glucose-induced electrical activity in mouse pancreatic B-cells.
Acetylcholine (1-10 microM) depolarized the membrane and stimulated glucose-induced bursts of electrical activity in mouse pancreatic B-cells. The acetylcholine effects were mimicked by muscarine while nicotine had no effect on membrane potential. Pirenzepine, an antagonist of the classical M1-type muscarinic receptors, but not gallamine (1-100 microM), an antagonist of the classical M2-type receptors, antagonized the acetylcholine action on glucose-induced electrical activity (IC50 = 0.25 microM). Bethanechol, an agonist of the classical M2-type muscarinic receptors, was approximately 100 times less effective than acetylcholine in stimulating the electrical activity. In addition, acetylcholine (1 microM) induced a marked increase (25%) in input resistance to the B-cell membrane. The results indicate that acetylcholine exerted its effects on the B-cell membrane by inhibiting K+ conductance via activation of a muscarinic receptor subtype distinct from the classical M2-type receptor.
Santos
R M
RM
Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892.
Rojas
E
E
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009116:Muscarine / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000502:physiology*; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000502:physiology*
D001626:Bethanechol Compounds; D011976:Receptors, Muscarinic; D018723:Bethanechol; D010890:Pirenzepine; D009116:Muscarine; D005947:Glucose; D000109:Acetylcholine