Functional characterization of muscarinic receptors in rat parotid acini.
The muscarinic agonist, carbamylcholine, stimulated amylase secretion in rat parotid acini 6-fold, the 86Rb efflux 5-fold, the 45Ca efflux 5-fold and the accumulation of inositol monophosphate, bisphosphate, trisphosphate and tetrakisphosphate 4-, 4-, 3- and 3-fold, respectively. The EC50 of carbamylcholine on these parameters were 0.4, 0.5, 1.3, 12, 12, 6 and 9 microM, suggesting spareness between phospholipase C activation and amylase secretion. These muscarinic responses were inhibited by four muscarinic antagonists with an order of potency on all parameters and on receptor occupancy (using N-[methyl-3H]scopolamine as a tracer): atropine greater than hexahydrosiladifenidol greater than pirenzepine greater than AF-DX 116. The pA2 of these antagonists on carbamylcholine-stimulated amylase secretion were 9.72 for atropine, 8.14 for hexahydrosiladifenidol, 7.16 for pirenzepine and 6.22 for AF-DX 116, indicating that the parotid muscarinic receptors were of an M2 subtype 83-fold more sensitive to hexahydrosiladifenidol than to AF-DX 116.
Dehaye
J P
JP
Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
Marino
A
A
Soukias
Y
Y
Poloczek
P
P
Winand
J
J
Christophe
J
J
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002132:Calcium Radioisotopes; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D019832:N-Methylscopolamine; D010306:Parotid Gland / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012414:Rubidium Radioisotopes; D012602:Scopolamine Derivatives / Q000378:metabolism
D002132:Calcium Radioisotopes; D007295:Inositol Phosphates; D011976:Receptors, Muscarinic; D012414:Rubidium Radioisotopes; D012602:Scopolamine Derivatives; D002217:Carbachol; D000681:Amylases; D019832:N-Methylscopolamine