Oxytocin action: lack of correlation between receptor number and tissue responsiveness.
Brattleboro rats exhibit diabetes insipidus (DI) because of a genetic autosomal recessive defect in the synthesis of vasopressin; oxytocin is synthesized normally. Preliminary work suggests that elevated circulating oxytocin levels may compensate for the absence of vasopressin. To evaluate the consequences of presumed elevations of oxytocin levels, oxytocin binding and tissue responsiveness have been measured in the uterus and epididymal fat cells of homozygous-DI (HoDI) and heterozygous-DI (HeDI) animals and Sprague-Dawley and Long-Evans controls. Surprisingly, whereas membranes from HoDI rat uteri exhibited an 85% reduction in oxytocin binding, the biological response (contraction) to oxytocin was indistinguishable from the uteri of HeDI or Sprague-Dawley animals. The uterine response to carbachol was also normal in HoDI rats. In contrast, in adipocytes from HoDI animals, the biological response to oxytocin (glucose oxidation) was abolished, whereas the binding of oxytocin was normal; insulin-stimulated glucose oxidation was, however, normal. These results indicate that receptor binding, while critical to hormone action, is not the sole determining factor. With oxytocin action, postreceptor mechanisms are most important in determining oxytocin responsiveness.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002452:Cell Count; D002462:Cell Membrane / Q000378:metabolism; D003919:Diabetes Insipidus / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D007700:Kinetics; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018045:Receptors, Oxytocin; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D011956:Receptors, Cell Surface; D018045:Receptors, Oxytocin; D010121:Oxytocin; D002217:Carbachol; D005947:Glucose