Evidence for peptidase activity in the rat intestine.
1. Cholinergic contraction was induced in segments of rat jejunum by transmural stimulation (10 Hz, 1 ms for 8 s). The synthetic delta-opiate agonist, DADLE (100 nM), caused a prolonged inhibition of the cholinergic response. 2. The naturally occurring opioid peptides, dynorphin A (1-13) (200 nM), leu-enkephalin (400 nM), met-enkephalin (200 nM) and the synthetic delta-agonist, DSLET (30 nM), also caused large inhibitions 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 of peptidase inhibitors consisting of bestatin (30 microM), thiorphan (10 microM), captopril (10 microM) and L-leucyl-L-leucine (2 mM). 4. The enkephalinase inhibitor, thiorphan (10 microM), 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 peptidase inhibitors did not significantly alter the cholinergic contraction in the absence of opioid peptides. 5. It is concluded that peptidases, including enkephalinase, are present in the rat intestine. However, the model presently described does not release functional amounts of endogenous opioid peptides, nor does it become tolerant to the effect of stimulating its delta-opioid receptors.
Hancock
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School of Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Vic., Australia.
Coupar
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D000595:Amino Acid Sequence; D000818:Animals; D004361:Drug Tolerance; D004744:Enkephalin, Methionine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007422:Intestines / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D018847:Opioid Peptides / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015244:Thiorphan / Q000494:pharmacology; D013997:Time Factors
D018847:Opioid Peptides; D011480:Protease Inhibitors; D004744:Enkephalin, Methionine; D015244:Thiorphan; D010447:Peptide Hydrolases