SK&F 105494, a V2-vasopressin receptor antagonist, blocks oxytocin receptors in porcine myometrium
Abstract
AIM: To study the effects of SK & F 105494 (SK & F), a V2-vasopressin receptor antagonist, on lypressin (Lyp)- and oxytocin (Oxy)-induced increases in myometrial contractility.
METHODS: Uterine strips isolated from sows in the luteal phase of the estrous cycle were used to study the contractility. The receptor binding assays were performed to study the Oxy receptor blocking activity.
RESULTS: Lyp and Oxy caused a concentration-dependent increase in myometrial contractility with EC50 of 50 +/- 14 nmol.L-1 and 170 +/- 32 pmol.L-1, respectively. SK & F 30-300 nmol.L-1 antagonized the contractile effects of Lyp and Oxy in a concentration-dependent manner. When the concentration-dependent inhibition of [3H] Oxy binding by SK & F was compared with Lyp and L-366948 [(cyclo-(L-Pro-D-2-naphthyl-Ala-L-lle-D-pipecolic acid-L-pipecolic acid-D-His)], a potent antagonist specific for Oxy receptors, the Ki values for SK & F, Lyp, and L-366948 were 1.73 +/- 0.32, 14.36 +/- 1.73, and 1.79 +/- 0.35 nmol.L-1, respectively.
CONCLUSION: SK & F has a potent Oxy receptor blocking activity in addition to its known V2-receptor blocking activity.
Keywords:
METHODS: Uterine strips isolated from sows in the luteal phase of the estrous cycle were used to study the contractility. The receptor binding assays were performed to study the Oxy receptor blocking activity.
RESULTS: Lyp and Oxy caused a concentration-dependent increase in myometrial contractility with EC50 of 50 +/- 14 nmol.L-1 and 170 +/- 32 pmol.L-1, respectively. SK & F 30-300 nmol.L-1 antagonized the contractile effects of Lyp and Oxy in a concentration-dependent manner. When the concentration-dependent inhibition of [3H] Oxy binding by SK & F was compared with Lyp and L-366948 [(cyclo-(L-Pro-D-2-naphthyl-Ala-L-lle-D-pipecolic acid-L-pipecolic acid-D-His)], a potent antagonist specific for Oxy receptors, the Ki values for SK & F, Lyp, and L-366948 were 1.73 +/- 0.32, 14.36 +/- 1.73, and 1.79 +/- 0.35 nmol.L-1, respectively.
CONCLUSION: SK & F has a potent Oxy receptor blocking activity in addition to its known V2-receptor blocking activity.