オルニプレシン CAS:3397-23-7

Ornipressin is a synthetic derivative of vasopressin (arginine-8-vasopressin) in which ornithine is substituted for arginine at the 8 position. The basicity of the amino-acid residue at position 8 of the vasopressin molecule determines its pressor and anti-diuretic effect. Ornithine, being both less basic and a short-chain amino-acid, reduces the binding of ornipressin to the receptors in the distal tubule of the nephron without impairing its binding to the receptors in the vascular smooth muscle which mediate vasoconstriction. したがって, ornipressin has minimal antidiuretic activity whilst maintaining equipotent vasoconstrictor activity as the natural hormone, vasopressin.

Ornipressin, which has a high affinity for V_1あ receptors , activates Gs proteins, which stimulate phospholipase C and result in a breakdown of membrane lipids to inositol triphosphate (IP₃) and diacylglycerol (DAG); IP₃ releases calcium from the endoplasmic reticulum, thus increasing cytosolic calcium, while DAG activates protein kinase C which phosphorylates cellular proteins. This cascade of biochemical reactions leads to sustained vasoconstriction. However, at high concentrations (>0.1 IU mL⁻¹), ornipressin binds to the V₂ receptors when the V_1あ receptors are fully saturated. Activation of V₂ receptors results in an increase in cyclic AMP which leads to vasodilatation, a paradoxical effect demonstrated by Fruhstorfer and Heisler.