EFFECTS OF MET-ENKEPHALIN ON THE MECHANICAL-ACTIVITY AND DISTRIBUTIONOF MET-ENKEPHALIN-LIKE IMMUNOREACTIVITY IN THE CAT LARGE-INTESTINE

The effects of Met-enkephalin on the spontaneous and electrically evok ed activity were investigated in longitudinal and circular strips isol ated from different regions of the large intestine, i.e., proximal col on, distal colon and rectum. Met-enkephalin induced dose-dependent con tractile responses which were reversibly blocked by naloxone (10(-6) M ). In all longitudinal strips and in the circular strips of the rectum , the effects of Met-enkephalin were prevented by TTX (10(-7) M), demo nstrating their neurogenic nature. In the circular strips from the col on, Met-enkephalin induced contractile responses after TTX, proving th e existence of smooth muscle opioid receptors. The comparison between the EC50 values of Met-enkephalin showed that the opioid receptors in the different regions have different sensitivity to Met-enkephalin. wh ile the opioid receptors in the longitudinal and circular layers of th e same region have equal affinity. Atropine (10(-6) M) and guanethidin e (10(-6) M) did not alter significantly the EC50 values, showing that the neurogenic effects of Met-enkephalin on the spontaneous activity involve mainly nonadrenergic, noncholinergic (NANC) neurotransmitter m echanisms. When the preparations were stimulated electrically, Met-enk ephalin (10(-9) M) suppressed the cholinergic components of the respon ses. Met-enkephalin-containing nerve fibers were found in the myenteri c plexus of the three intestinal regions. In the colon, where direct s mooth muscle effects were observed, fibers containing Met-enkephalin-l ike immunoreactivity were found to go deep into the circular layer, su ggesting that they could supply Met-enkephalin input to the smooth mus cle cells.