INSULIN-RECEPTOR DOWN-REGULATION IN ISOLATED HEPATOCYTES OF RIVER LAMPREY (LAMPETRA-FLUVIATILIS)

Insulin receptor downregulation in the isolated hepatocytes of lamprey (Lampetra fluviatilis) was studied at the ambient temperature for thi s species. Preincubation of hepatocytes with 10(-9)-10(-8) M unlabeled insulin decreased insulin binding capacity to 43, 37, and 34% at 4, 1 5, and 25 degrees, respectively. Preincubation of hepatocytes in the p resence of 10(-10) M unlabeled insulin had no effect on the I-125-insu lin binding. The maximal decrease in the I-125-insulin binding was rea ched after 10 min of preincubation and was then maintained at a consta nt level for 2 hr. Competitive binding assays demonstrated that preinc ubation with unlabeled insulin resulted in a 45% decline in the number of binding sites. In rat adipocytes and frog hepatocytes used for the comparison, preincubation with insulin caused a 65% decrease in cell- surface receptors, while intracellular (internalized receptors) increa sed proportionally. In contrast, in the lamprey hepatocytes both cell- surface and intracellular receptors decreased. We conclude that insuli n receptors of the lamprey hepatocytes could be downregulated at the a mbient temperature for the species and at the physiological concentrat ions of insulin (10(-9)-10(-8) M). (C) 1995 Academic Press, Inc.