Vasopressin is thought to play an important role, not only in the metabolism of water and
electrolytes, but also in the regulation of renal hemodynamics. This year, great progress has been achieved in molecular biology of
vasopressin receptors. First, the cloning of a
complementary DNA, encoding the rat liver V1a
arginine vasopressin receptor, was reported. The liver
cDNA encodes a
protein with seven putative transmembrane domains, which binds
arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The
messenger RNA, corresponding to the
cDNA, is distributed in rat tissues, known to contain V1a receptors. Second, the cloning of a
complementary DNA encoding the rat kidney V2
arginine vasopressin receptor was also successful. The kidney
cDNA encodes a
protein with a transmembrane topography characteristic of
G protein-coupled receptors. The receptor
messenger RNA is detected only in the kidney. Last year, an orally active and specific
vasopressin V1 receptor antagonist,
OPC-21268 was first reported. The i.v. or p.o. administration of
OPC-21268 dose-dependently inhibited
vasopressin-induced vasoconstriction, while that induced by
angiotensin II was not affected.
OPC-21268 may have clinical potentials in certain hypertensive cardiovascular disorders. In addition, an orally active and specific
vasopressin V2 receptor antagonist,
OPC-31260 was also reported.
Oral administration of
OPC-31260 inhibited antidiuretic action of
arginine vasopressin.
OPC-31260 is thought to be useful in the treatment of certain disorders, such as the syndrome of inappropriate secretion of ADH (
SIADH).