Reduction in hepatic but not in renal and vascular vasopressin receptor number in hyperinsulinemic mice and rats.
Hepatic plasma membranes of female obese mice C57 BL-6 orl ob/ob (ob/ob mice) completely lack vasopressin (VP) receptors of the V1 type whereas kidney VP receptors are normally expressed and functionally coupled to adenylate cyclase. To discover if these alterations are linked to a genetic defect of the V1 receptor, we have studied the binding of VP on liver and kidney membranes of two other models, female diabetic mice C57 BL-6 orl db/db (db/db mice) and female Zucker rats Fatty/orl fa/fa (fa/fa rats), which exhibit different temporal pattern of obesity, hyperinsulinemia and insulin resistance. In addition, since VP is known to exert its vascular response through stimulation of V1 receptors, we have studied the reactivity of VP of isolated tail artery in the three different models, ob/ob and db/db mice and fa/fa rats, and in their respective controls. In all cases, VP kidney receptors and VP vascular reactivity are normal. db/db mice exhibit a marked decrease in hepatic VP receptors whereas a 50% decrease was observed in 32 week fa/fa rats. Angiotensin II and prazosin binding sites are still present as well as the adenylate cyclase response to glucagon. These results suggest that the specific alteration in liver VP receptors is not related to a defect in V1 receptor genetic expression but is specific for liver and appears to parallel the level of hyperinsulinemia and/or insulin resistance.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D011945:Receptors, Angiotensin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017483:Receptors, Vasopressin; D014667:Vasopressins / Q000494:pharmacology
D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D017483:Receptors, Vasopressin; D014667:Vasopressins; D010656:Phenylephrine; D005934:Glucagon; D000262:Adenylyl Cyclases