M3 muscarinic receptors on rat colonocytes are coupled to particulate guanylate cyclase activation.
The ability of muscarinic receptor antagonists to compete with (-)-[3H]quinuclidinyl benzilate ([3H]QNB) binding was compared with their ability to block carbachol-mediated stimulation of particulate guanylate cyclase activity in rat colonocytes. The binding of [3H]QNB to membranes was inhibited by antagonists with the following rank order of potencies (inhibitory constants, nM): atropine (2.5) approximately 4-diphenylacetoxy-N-methylpiperidine iodide (4-DAMP) [4.6] >> pirenzepine (121) > methoctramine (385). 4-DAMP (IC50 = approximately 10 nM) was also more potent in blocking carbachol-induced stimulation of guanylate cyclase activity than either pirenzepine (IC50 = approximately 700 nM) or methoctramine (IC50 = approximately 1500 nM).
Khare
S
S
Department of Medicine, University of Chicago, IL 60637.
Wilson
D M
DM
Tien
X Y
XY
Brasitus
T A
TA
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D018727:Muscarinic Antagonists; D010890:Pirenzepine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D002217:Carbachol; D006162:Guanylate Cyclase