AGONISTIC AND ANTAGONISTIC PROPERTIES OF ANGIOTENSIN ANALOGS AT THE AT2-RECEPTOR IN PC12W CELLS

Despite some recent reports describing the effects of AT2 receptor selective ligands in vitro and in vivo, the physiological function of this receptor is still a matter of debate. This problem stemms amongst others from the difficulty in interpreting results from in vivo experiments with drugs of which it is not known whether they act as agonists or antagonists. We reported earlier that angiotensin II inhibits basal and atrial natriuretic peptide stimulated particulate guanylate cyclase activity through AT2 receptors in PC12W cells [1]. We have used this parameter in intact PC12W cells in order to determine the pharmacological properties of different widely used angiotensin receptor ligands. We found CGP 42112 to behave as a full agonist in this system, whereas PD 123319 and Sar1Ile8angiotensin II act as antagonists. As expected, the AT1 antagonist losartan did not affect this response.