Effects of ethanol and inhibitors of its metabolism on the circulating levels of Met-enkephalin in greyhounds.
The mechanisms involved in the release of Met-enkephalin-like immunoreactivity (MLI) into the circulation following oral administration of ethanol and chlorpropamide were investigated in dogs. The origin of plasma MLI and the sites where it may be metabolized were also studied. Moreover, the molecular nature of circulating MLI was characterized. In conscious animals oral administration of ethanol (0.15 ml/kg) led to a significant (P less than 0.01) rise in plasma MLI concentrations in chlorpropamide-pretreated animals from a basal level of 43 +/- 6 (mean +/- S.E.M.) to a peak of 66 +/- 8 ng/l. Similar rises in MLI concentrations were observed following administration of ethanol with disulfiram and ethanol with chlorpropamide and captopril. In contrast, the administration of ethanol alone or ethanol with 4-methylpyrazole resulted in a decrease in plasma MLI concentrations. Comparisons of two different doses of i.v. acetaldehyde, the first metabolite of ethanol, showed that plasma MLI concentrations rose significantly (P less than 0.05) only after the larger dose (8 mg/kg), rising from 45 +/- 7 to 81 +/- 18 ng/l. These results suggest that acetaldehyde is the active component in the chlorpropamide + ethanol-induced MLI secretion. Plasma MLI was also measured following acetaldehyde infusion in adrenalectomized dogs with and without hexamethonium treatment. Acute bilateral adrenalectomy resulted in a decrease (P less than 0.05) in plasma MLI concentrations, but the levels remained detectable. Moreover, subsequent acetaldehyde infusion led to rises in plasma MLI similar to those observed in animals with intact adrenals. These MLI responses were not altered by the concurrent i.v. administration of hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)
Medbak
S
S
Department of Pharmacology, Medical College of St Bartholomew's Hospital, London.
Mason
D F
DF
Rees
L H
LH
D000079:Acetaldehyde / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects / Q000378:metabolism; D002747:Chlorpropamide / Q000494:pharmacology*; D004285:Dogs; D004744:Enkephalin, Methionine / Q000097:blood*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000431:Ethanol; D004744:Enkephalin, Methionine; D000079:Acetaldehyde; D002747:Chlorpropamide