Excitatory effect of morphine and opioid peptides in the rat isolated colon

Morphine and the opioid peptides cause isolated segments of rat colon to contract and relax rhythmically. This study re-examines two hypotheses to explain this phenomenon: Release of 5-hydroxytryptamine (5-HT)/acetylcholine by morphine or inhibition of a tonically active non-adrenergic, non-cholinergic (NANC) inhibitory mechanism. Rhythmic contractions induced by morphine (5 x 10(-6) M) were naloxone sensitive (10(-6) M) but unaffected by methysergide (10(-6) M), atropine (10(-6) M) or pretreatment of rats with p-chlorophenylalanine (200 mg kg-1 i.p. for four days) which lowered the 5-HT level in the colon from 3.73 +/- 0.83 mg g-1 in controls to 0.41 +/- 0.06 mg g-1 (P less than 0.001). The pattern of rhythmic contractions produced by morphine was unlike those produced by 5-HT (5 x 10(-6) M), acetylcholine (5 x 10(-6) M) or potassium chloride (30 mM). Tetrodotoxin (10(-6) M), apamin (10(-8) M), clonidine (2 x 10(-8) M), phentolamine (10(-5) M) or oxprenolol (10(-5) M) caused rhythmic contractions which were unaffected by naloxone. Clonidine contractions were inhibited by yohimbine (10(-7) M) but not by prazosin (10(-6) M). Electrical field stimulation at the peak of a contraction induced by morphine, apamin or clonidine, produced an inhibitory response which was unaffected by atropine, phentolamine, propranolol and guanethidine (all 10(-5) M). It persisted in colon segments from the rats with reserpine or 6-hydroxydopamine. These results suggest that neither the 5-HT/acetylcholine hypothesis nor inhibition of the NANC mechanism adequately explains the excitatory effect of morphine in the rat colon.