The response of the intestinal mucosa to prostaglandin E2 during withdrawal from morphine.
Experiments were designed to determine whether the diarrhoea characteristic of morphine withdrawal results from an enhanced sensitivity of the intestinal mucosa to PGE2. Rats (250-300 g) were made morphine-dependent by subcutaneous injection of an emulsion releasing 300 mg morphine HCl over 48 h. In-vivo, the transintestinal potential difference (PD) responses to PGE2 (4.6-46 micrograms kg-1 i.v.), which reflect increased Cl secretion, were significantly larger in withdrawn (morphine emulsion, 10 mg kg-1 naloxone s.c.) compared with non-dependent animals (emulsion only, naloxone s.c., P less than 0.05). Muscle-stripped intestinal sheets from dependent animals incubated with naloxone (10(-5) mol L-1) in-vitro did not demonstrate a greater electrical response (PD, short circuit current) to PGE2 (1.4 x 10(-6) mol L-1) than sheets taken from non-dependent animals. In-vitro preparations from animals withdrawn in-vivo did not respond differently from tissue taken from non-dependent animals (naloxone 10 mg kg-1 s.c., 10(-4) mol L-1 in medium, in both groups). This occurred in whole sheets of intestine as well as sheets without attached muscle. Jejunal fluid absorption in-vivo was lower in withdrawn animals than in non-dependent animals. However, the responses to intra-arterial infusion of PGE2 were similar in both groups with 2 micrograms min-1 inhibiting absorption and 4 micrograms min-1 inducing secretion. In-vivo, PGE2-induced Cl secretion appears to be enhanced during withdrawal although net fluid transport is not altered, suggesting different effects of the withdrawal process on the electrogenic Cl secretory and neutral NaCl absorptive mechanisms.
D000818:Animals; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology; D015232:Dinoprostone; D004566:Electrodes; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D011458:Prostaglandins E; D009020:Morphine; D015232:Dinoprostone