Selective stimulation of colonic motor response to a meal by sigma ligands in dogs.
The influence of central vs. peripheral administration of sigma ligands (dl- and l-N-allylnormetazocine, 1-3-di-o-tolylguanidine, (+) cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene and phencyclidine on colonic motility was investigated in fasted and fed dogs equipped with strain-guage transducers implanted on proximal and transverse colon. When injected intravenously at a dose of 0.25 mg/kg just before feeding, dl- or d-N-allylnormetazocine, 1-3-di-o-tolylguanidine, and (+) cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene (but not phencyclidine) enhanced the colonic motor response to a meal by increasing the 0-4-hour motility indexes from 64.1%-159.3% in both the proximal and transverse colon but had no effect on colonic motility in fasted animals or animals injected intracerebroventricularly. The motor-stimulatory effects of d-N-allylnormetazocine (1 mg/kg), 1-3-di-o-tolylguanidine (0.25 mg/kg), and (+) cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene (1 mg/kg) were abolished after previous treatment with haloperidol (0.5 mg/kg, intravenous) but not after sulpiride (0.1 mg/kg) or (+) R-(+)-8-chloro-2,3,4,5-tetrahydro-3- methyl-5-phenyl-1-H-3-benzozepine-OH. Prazosin (0.1 mg/kg, intravenous) and 1-methyl-3-(2-indolyl)amino-5-phenyl-3H-1,4-benzodiazepin-2-one (0.01 mg/kg) also suppressed the enhancement of the colonic motor response to eating induced by d-N-allylnormetazocine, 1-3-di-o-tolylguanidine, and (+)cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene whereas naltrexone did not affect their effects. It is concluded that d-N-allylnormetazocine, 1-3-di-o-tolylguanidine, and (+)cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene stimulate the postprandial colonic motility in dogs by acting selectively on sigma receptors located peripherally and probably by affecting the release of cholecystokinin octapeptide through a central adrenergic mechanism.
Junien
J L
JL
Department of Pharmacology INRA, Toulouse, France.
Gue
M
M
Pascaud
X
X
Fioramonti
J
J
Bueno
L
L
D000818:Animals; D002934:Cinnamates / Q000494:pharmacology; D003106:Colon / Q000187:drug effects*; D003521:Cyclopropanes / Q000494:pharmacology; D004285:Dogs; D004336:Drug Antagonism; D004435:Eating / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma; D013237:Stereoisomerism
D002934:Cinnamates; D003521:Cyclopropanes; D006146:Guanidines; D011957:Receptors, Opioid; D017480:Receptors, sigma; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine; C050232:1,3-ditolylguanidine; C065310:igmesine