Atypical angiotensin II receptors coupled to phosphoinositide turnover/calcium signalling in catfish hepatocytes

摘要

In catfish (Ictalurus punctatus) hepatocytes angiotensin II induced an immediate increase in cytosolic Ca2+ concentration. Other angiotensin analogues also induced this effect including: human angiotensin II, fish angiotensin II, human angiotensin III, human angiotensin I, fish angiotensin I and saralasin. CGP 42112A induced a very small effect at the highest concentration tested and angiotensin IV was without effect. Angiotensin II also increased the resynthesis of phosphatidylinositol and the production of IP3. These physiological effects were not blocked by losartan (AT1-selective antagonist) or PD 123177 (AT2-selective antagonist). [125I]Angiotensin II bound to liver plasma membranes in a saturable fashion with high affinity (KD 2.7 nM) and a Bmax of 185 fmol/mg of protein. Binding competition experiments showed the following order of potency: human angiotensin II=fish angiotensin II>human angiotensin III≥human angiotensin I=fish angiotensin I. These sites were insensitive to losartan or PD 123177. The data indicate that the angiotensin II receptors expressed in catfish hepatocytes are coupled to the phosphoinositide turnover/calcium mobilization signal transduction pathway and are atypical receptors, i.e., pharmacologically distinct from mammalian AT1 and AT2 receptors.