title: Stimulatory effects of HSR-803 on ileal motor activity.
abstract: Stimulatory effects of HSR-803 on intestinal motor activity in vitro were studied in guinea pig ileum. HSR-803 (1 x 10(-6)-1 x 10(-4) M) increased the amplitude of longitudinal muscle contractions and increased the frequency of peristalsis in isolated segments of guinea pig ileum. The stimulatory effect in amplitude and not frequency was abolished by 1 x 10(-6) M atropine. In the Magnus method with ileal segments, HSR-803 (1 x 10(-7) - 1 x 10(-4) M) produced contractions concentration-dependently, which were inhibited by atropine (1 x 10(-8) and 3 x 10(-8) M) and 3 x 10(-7) M tetrodotoxin (TTX). In the [3H]-quinuclidinyl benzilate (QNB) binding experiment with ileal smooth muscle, HSR-803 had low affinity for acetylcholine (ACh) receptors (pKi = 4.47 +/- 0.04). In addition, HSR-803 failed to increase the spontaneous release and the electrical stimulation-induced [3H]ACh release in ileal smooth muscle. On the other hand, HSR-803 (1 x 10(-5) M) enhanced contractions induced by ACh, but had no effect on contractions induced by carbachol, which is not hydrolyzed by acetylcholinesterase (AChE). In conclusion, HSR-803 stimulated ileal motor activity. However, HSR-803 had low affinity for ACh receptors and had no influence on ACh release. It is likely that HSR-803 stimulated motor activity mainly due to prevention of ACh hydrolysis.
authors.affiliation: Central Research Laboratories, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Morikawa
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Gomi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D010528:Peristalsis / Q000187:drug effects*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D001549:Benzamides; D001593:Benzyl Compounds; D002800:Cholinesterase Inhibitors; D011950:Receptors, Cholinergic; C064878:N-(4-(2-(dimethylamino)ethoxy)benzyl)-3,4-dimethoxybenzmide; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D000109:Acetylcholine