Activation of propylbenzilylcholine mustard-sensitive muscarinic cholinoceptors more effectively utilizes cytosolic Ca2+ for contraction in guinea-pig intestinal smooth muscle.
A 50-min treatment of longitudinal smooth muscle of guinea-pig ileum with propylbenzilylcholine mustard (PrBCM, 3 x 10(-6) M) irreversibly inhibited the responses elicited by carbachol. However, a 90-min treatment with PrBCM had no further significant inhibitory effect on the responses to carbachol, suggesting that there are two subtypes of muscarinic cholinoceptors, PrBCM-sensitive and PrBCM-insensitive receptors. Carbachol caused a rapid increase in cytosolic Ca2+ concentrations ([Ca2+]i), which was followed by a rapid increase in muscle tension in both untreated and PrBCM-treated preparations. There was a positive correlation between [Ca2+]i (R340/380) and tension developed in response to carbachol. A regression line for the two responses was obtained in each preparation. The slope of the line obtained with untreated preparations was steeper than that obtained with PrBCM-treated preparations. These data suggest that, upon activation, PrBCM-sensitive receptors use cytosolic Ca2+ more effectively than PrBCM-insensitive receptors.
Takayanagi
I
I
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Kiuchi
Y
Y
Ohtsuki
H
H
Harada
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D016257:Fura-2; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011438:Propylbenzilylcholine Mustard / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D013050:Spectrometry, Fluorescence
D011950:Receptors, Cholinergic; D011438:Propylbenzilylcholine Mustard; D002217:Carbachol; D002118:Calcium; D016257:Fura-2