EXPRESSION OF MUSCARINIC RECEPTOR SUBTYPES IN RAT GASTRIC SMOOTH-MUSCLE - EFFECT OF M3 SELECTIVE ANTAGONIST ON GASTRIC-MOTILITY AND EMPTYING

Expression of muscarinic receptor subtypes in rat gastric smooth muscl e was examined with reverse transcriptase-polymerase chain reaction (R T-PCR). Under the condition for detecting the messages of m1-m4 subtyp es in brain, atrium, and gastric mucosa, only the fragments of m2 and m3 subtypes were amplified with RNA prepared from rat gastric smooth m uscles. Furthermore, the amplified fragments were digested by restrict ion enzymes, reconfirming that the predicted size products of m2 and m 3 contain the partial DNA sequences of m2 and m3 subtypes, respectivel y. We measured gastric motility in rats with a pressure transducer sys tem under the continuous venous infusion of the muscarinic antagonists atropine and butylscopolamine (nonselective), AF-DX 116 (M2), zamifen acine (M3), and glucagon. Heart rate was monitored simultaneously in t he tail. Gastric motility was inhibited in the presence of glucagon an d zamifenacine without alteration of heart rate, whereas there was no inhibition in the presence of AF-DX 116 even after the augmentation of heart rate was observed. Gastric emptying was also suppressed in the presence of zamifenacine, which had an effect comparable with that of atropine, butylscopolamine, and glucagon. These results indicate that the activation of the M3 subtype in gastric smooth muscle causes its c ontraction, and the M3 selective antagonist could be a potentially use ful drug without an adverse effect on the heart for radiological and e ndoscopic examination in the upper gastrointestinal tract.