Abstract:
:The amidated beta-casomorphin morphiceptin Tyr-Pro-Phe-Pro-NH2 is an opioid peptide isolated from bovine milk beta-casein digests whose physiological significance remains unclear. Opiates are known to modify intestinal electrolyte transport by acting on receptors located on the serosal side of the intestine. The aim of the present study was to determine under what conditions morphiceptin can act from the luminal side. When added to the serosal side of untreated rabbit ileum in an Ussing chamber in vitro, 10(-3) M morphiceptin acted through an opiate mechanism to reduce simultaneously short-circuit current (delta Isc = 0.33 +/- 0.07 muEq.hr-1.cm-2) and stimulate net Na and Cl absorption (delta JnetNa = 1.62 +/- 0.11 and delta JnetCl = 2.07 +/- 0.08 muEg.hr-1.cm-2). After mucosal addition under the same conditions, morphiceptin was degraded without any opiate action on electrolyte transport. Pretreatment of the ileum by 10(-3) M diisopropylfluorophosphate, which inhibited brush-border dipeptidylpeptidase IV, prevented mucosal degradation of morphiceptin. Under these conditions, morphiceptin was able, when added mucosally, to cross the epithelium intact (Jm----s = 1.8 +/- 0.16 nmole.hr-1.cm-2) and to stimulate electrolyte absorption by means of an opioid mechanism (delta Isc = 0.22 +/- 0.02 muEq.hr-1.cm-2). These results showed that the action of morphiceptin from the lumen depends on its transfer intact to the serosal side of the intestine where the opiate receptors are located. The limiting step in this transfer is at the brush-border membrane, where dipeptidylpeptidase IV in particular seems to play a major role.
journal_name
Peptidesjournal_title
Peptidesauthors
Mahe S,Tome D,Dumontier AM,Desjeux JFdoi
10.1016/0196-9781(89)90074-0subject
Has Abstractpub_date
1989-01-01 00:00:00pages
45-52issue
1eissn
0196-9781issn
1873-5169pii
0196-9781(89)90074-0journal_volume
10pub_type
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