COMPARATIVE EFFECTS OF ARGININE VASOPRESSIN AND OXYTOCIN IN CELL-CULTURE SYSTEMS

Arginine vasopressin (AVP) and oxytocin (OXT) induced contraction in cultured vascular smooth muscle cells (VSMC) and glomerular mesangial cells (GMC). The contractile response of AVP and OXT was paralleled by Ca2+ mobilization as assessed by Ca-45(2+) efflux in a dose-dependent manner. The effects of AVP were blocked by pretreating VSMC and GMC with a V1 antagonist. OXT-stimulated effects, however, were not affected by preexposure of VSMC and GMC to an OXT antagonist but were inhibited by the V1 antagonist. Competition studies demonstrated displacement of [H-3]AVP from its receptors by unlabeled AVP, the V1 antagonist, and high doses of OXT. The OXT antagonist was the least effective in displacing [H-3]AVP. Thus occupancy of the V1 receptor by OXT may initiate signal transduction and contraction in VSMC and GMC in a manner qualitatively similar to that of the AVP agonist. Cultured myometrium cells (MMC) also contracted in response to AVP and OXT. Moreover, Ca-45(2+) efflux increased in response to both hormones in a dose-dependent manner. AVP-stimulated contraction and Ca-45(2+) efflux were blocked in MMC by pretreatment with V1 antagonist. OXT-induced effects were inhibited by the OXT antagonist but not by the V1 antagonist. Binding experiments showed that [H-3]AVP was displaced equally by unlabeled AVP and V1 antagonist. Very high concentrations of OXT antagonist also demonstrated displacement. Thus using V1 and OXT antagonists, the present in vitro results indicate 1) AVP induces contraction in VSMC and GMC by a V1 receptor, 2) high doses of OXT occupy the V1 receptor in VSMC and GMC and thereby induce contraction, and 3) AVP stimulates MMC contraction via the V1 receptor, whereas 4) the OXT effect in MMC is mediated by an OXT receptor.