EVIDENCE FOR PEPTIDASE ACTIVITY IN THE RAT INTESTINE

1 Cholinergic contraction was induced in segments of rat jejunum by tr ansmural stimulation (10 Hz, 1 ms for 8 s). The synthetic delta-opiate agonist, DADLE (100 nM), caused a prolonged inhibition of the choline rgic response. 2 The naturally occurring opioid peptides, dynorphin A (1-13) (200 nM), leuenkephalin (400 nM), met-enkephalin (200 nM) and t he synthetic delta-agonist, DSLET (30 nM), also caused large inhibitio ns in the response. 3 Each of these peptides lost a significant amount of their original activity at 6 min, which was reduced by a mixture o f peptidase inhibitors consisting of bestatin (30 mu M), thiorphan (10 mu M), captopril (10 mu M) and L-leucyl-L-leucine (2 mM). 4 The enkep halinase inhibitor, thiorphan (10 mu M), significantly lengthened the time at which met-enkephalin was active, but not to the same extent as the mixture of peptidase inhibitors. However, the mixture of peptidas e inhibitors did not significantly alter the cholinergic contraction i n the absence of opioid peptides. 5 It is concluded that peptidases, i ncluding enkephalinase, are present in the rat intestine. However, the model presently described does not release functional amounts of endo genous opioid peptides, nor does it become tolerant to the effect of s timulating its delta-opioid receptors.