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Gillan MGC, Pollock D. 
“Investigation of the effects of drugs on morphine-induced contractions of the isolated colon of the rat”. 
Brit.J.Pharmacol.. 1976;57(3):444-45.
Morphine (M) causes some smooth muscle-containing tissue to contract. Whether or not M causes contractions depends on the dose, species and tissue examined. In dog intestine, M. produces contractions indirectly by releasing 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) (Burks,1973). This study sought to determine whether M had a similar effect in rat intestine. Effects of M were investigated by adding the drug to an organ bath containing 3-4 cm lengths of terminal colon suspended in oxygenated Krebs bicarbonate solution at 37ˇ. Responses of the colon were recorded isometrically, M (10-5M) produced an immediate contraction followed at Ca 1-min intervals by waves of contractions, which gradually decreased in amplitude. When the tissue had ceased responding to the 1st dose of M, addition of a 2nd dose was less effective in causing contractions. Prior additon of naloxone (5 x 10-6M) added after rhythmic activity had been initiated by M was less effective in inhibiting the contractions. M-induced contractions were not inhibited by atropine (10-4M), hexamethonium (10-4M) or tubocurarine (10-4M). Indeed, these drugs occasionally potentiated M-induced contractions. Unlike in dog intestine, responses produced by M in rat colon were dissimilar from thoľ produced by ACh or 5-MT. Effects of 5-HT antagonists on M-induced contractions were complex. Thus, lysergic acid diethylamide (3 x 10-7M) did not affect M-induced contractions but when administered alone, caused contractions similar to those produced by M. In contrast, cyproheptadine (3 x 10-5M) not only abolished M-induced contractions but also inhibited responses to carbachol (10-7M) and potassium (30 mM). M-induced contractions were potentiated by phentolamine (10-5M) and inhibited by noradrenaline (5 x 10-7M) or tyramine (3 x 10-5M). The dose of M required to produce contractions was lower in tissue from rats pretreated with reserpine (0.3 mg/kg daily for three days). In these tissues in which the frequency of spontaneous contraction was increased, tyramine (10-M) did not inhibit M-induced contractions. M-induced contractions were inhibited by adenosine (5 x 10 -6M), ATP (5 x 10-6M), papaverine (5 x 10-5 M) and by removing calcium from the bathing medium, but were unaffected by tetrodotoxin (3 x 10-7g/ml), which caused contractions similar to those produced by M.
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