CHARACTERIZATION OF ENDOTHELIN RECEPTORS IN STREPTOZOTOCIN-INDUCED DIABETIC RAT VAS-DEFERENS

As there is increasing evidence that diabetes induces changes in the p lasma levels of endothelins (ETs) and in the properties of ET receptor s in peripheral tissues, and as there are reports indicating the prese nce of significant amounts of ET receptors in mammalian vasa deferenti a, we studied possible alterations in ET receptor characteristics in t he vasa deferentia of the following groups of rats: 8 weeks diabetic ( D-8), 8 weeks age-matched control (C-8), 16 weeks diabetic (D-16), 16 weeks diabetic-insulin-treated (started 8 weeks after the onset of dia betes) (DI16), and 16 weeks age matched control (C-16). Diabetes was i nduced by the i.v. injection of 65 mg/kg streptozotocin (STZ). Diabeti c rats had hyperglycemia, hypoinsulinemia, glucosuria, polydipsia, and polyuria and had smaller vasa deferentia than control and diabetic-in sulin-treated animals. Receptor binding experiments with [I-125]ET-1 d emonstrated that the densities of ET receptors in vasa deferentia from D-8, C-8, D-16, DI16, and C-16 animals were 377 +/- 11, 255 +/- 24, 3 15 +/- 18, 210 +/- 12, and 214 +/- 7 fmol/mg of protein, respectively. [I-125]ET-1 binding to the ET receptors was inhibited by ET-1 (non-se lective), Ba 610 (ET(A) selective), ET-3 (ET(C) selective), and << IRL 1620 (ET(B) selective) with the following rank order of K-i values: E T-1 < BQ 610 < ET-3 << IRL 1620. The pharmacological profile of the ET receptors was similar in all groups and was consistent with the predo minance of the ET(A) receptor subtype in the rat vasa deferentia. Our data indicate that experimental diabetes up-regulates the density of E T receptors in the rat vasa deferentia and that the receptor up-regula tion is reversed by insulin treatment. Copyright (C) 1996 Elsevier Sci ence Inc.