Novokinin acetate exhibited an affinity for the AT2 receptor with Ki of 7 nM, and its antihypertensive and vasorelaxing activities were blocked by PD123319, an AT2 receptor antagonist.

AT2:7 nM(Ki)

Novokinin relaxed a mesenteric artery isolated from the spontaneously hypertensive rat (SHR) at 10(-5) M, and reduced SHR blood pressure at a dose of 0.1 mg/kg (po.) emulsified in 30% egg yolk[1].

The hypotensive effect of novokinin in normotensive mice was not observed in the AT2 receptor-knockout mice. Its antihypertensive and vasorelaxing activities in SHR were also blocked by CAY-10441, an antagonist of the IP receptor for prostaglandin I2 PGI2 suggesting that these activities are mediated by the AT2 receptor, followed by the prostaglandin I2-IP receptor pathway. Novokinin suppressed food intake after icv. or po. administration in mice. The anorexigenic activity was not observed in the AT2 receptor- knockout mice, but was observed in the AT 1 receptor-knockout mice. The anorexigenic activities of novokinin and angiotensin II were blocked by PD123319, and ONO-AE3-208, an antagonist of the EP4 receptor suggesting that the anorexigenic activities of the AT2 agonists are mediated by the PGE 2-EP4 receptor pathway downstream of the AT2 receptor. Novokinin given icv. in mice antagonized the antinociceptive effect of morphine[1].