Opiate and opiate antidiarrhoeal drug action on rat isolated intestine.
1. Stimulation of segments of rat jejunum (2.5, 5, 10, 20 and 40 Hz for 8 s) and ileum (10 Hz) resulted in a fast atropine-sensitive contraction during stimulation and a non-cholinergic after-contraction. Stimulation of segments with single pulses at 0.1 Hz had no effect. The colon (10 Hz) usually responded only with single large atropine-sensitive contractions. 2. The responses of the jejunum (2.5-40 Hz, 8 s) were unaffected by the mu-receptor ligands morphine (0.3 microM) and RX 783006 (0.3 microM) or the kappa-receptor ligand, ethylketocyclazocine (0.3 microM). The cholinergic contraction of the colon was unaffected by ethylketocyclazocine (0.3 microM), but was reduced slightly by morphine at high concentrations only. 3. The prototype delta-opiate receptor ligand D-Ala2-D-Leu5-enkephalin (DADLE; 30 nM) reduced the contraction during stimulation (2.5, 5, 10 and 20 Hz for 8 s) of the rat jejunum. The IC50 value for inhibition of the contraction elicited by stimulation at 10 Hz was 3.2 in the jejunum and was 12 nM in the ileum. Contractions of the colon were only slightly inhibited at a high concentration of DADLE (1 microM). 4. DADLE had no effect on contractions elicited by acetylcholine, at a concentration of up to 3 microM in segments of jejunum. Naloxone (1 microM) abolished the inhibitory effect of DADLE on the cholinergic contraction of the electrically stimulated jejunum. In addition, naloxone caused a large enhancement of control responses to stimulation. 5. Only high concentrations of the antidiarrhoeals loperamide and diphenoxylate inhibited the contraction elicited at 10 Hz in the jejunum (IC50, 1.3 and 7.1 microM, respectively) and ileum (loperamide IC50, 0.5 microM). The same concentrations of these drugs also inhibited the effect of exogenously added acetylcholine. A similar pattern of findings was made in the colon. 6. The results show marked differences in responses to transmural stimulation and to opiate drugs compared to those previously obtained from guinea-pig ileum.(ABSTRACT TRUNCATED AT 400 WORDS)
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Unit of Addictive Drug Research, School of Pharmacology, Victorian College of Pharmacy (Monash University), Parkville, Australia.
De Luca
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D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects
D000930:Antidiarrheals; D009294:Narcotics; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D016308:Enkephalin, Leucine-2-Alanine; D001285:Atropine; D000109:Acetylcholine