Expression of Muscarinic Receptor Subtypes (Effect of M3 Selective Antagonist on Gastric Motility and in Rat Gastric Smooth Muscle Emptying).

Expression of muscarinic receptor subtypes inrat gastric smooth muscle was examined with reversetranscriptase-polymerase chain reaction (RT-PCR). Underthe condition for detecting the messages of m1-m4 subtypes in brain, atrium, and gastric mucosa,only the fragments of m2 and m3 subtypes were amplifiedwith RNA prepared from rat gastric smooth muscles.Furthermore, the amplified fragments were digested by restriction enzymes, reconfirming that thepredicted size products of m2 and m3 contain the partialDNA sequences of m2 and m3 subtypes, respectively. Wemeasured gastric motility in rats with a pressure transducer system under the continuous venousinfusion of the muscarinic antagonists atropine andbutylscopolamine (nonselective), AF-DX 116 (M2),zamifenacine (M3), and glucagon. Heart rate wasmonitored simultaneously in the tail. Gastric motilitywas inhibited in the presence of glucagon andzamifenacine without alteration of heart rate, whereasthere was no inhibition in the presence of AF-DX 116even after the augmentation of heart rate wasobserved. Gastric emptying was also suppressed in thepresence of zamifenacine, which had an effect comparablewith that of atropine, butylscopolamine, and glucagon. These results indicate that the activation ofthe M3 subtype in gastric smooth muscle causes itscontraction, and the M3 selective antagonist could be apotentially useful drug without an adverse effect on the heart for radiological and endoscopicexamination in the upper gastrointestinaltract. [ABSTRACT FROM AUTHOR]