BRADYKININ STIMULATION OF PHOSPHOINOSITIDE HYDROLYSIS IN GUINEA-PIG ILEUM LONGITUDINAL MUSCLE

1 Bradykinin (BK)-induced contraction of ileal smooth muscle is assume d to be due to phosphoinositide hydrolysis but this has never been rep orted. We have investigated whether BK receptors are linked to this tr ansduction mechanism in guinea-pig ileum longitudinal muscle and deter mined whether these receptors are equivalent to those labelled in [H-3 ]-BK binding assays. 2 In membranes prepared from longitudinal muscle, [H-3]-BK bound to a single class of sites with high affinity. Charact erization of the binding with BK analogues indicated that the radiolig and selectivity labelled a B2 type receptor. 3 BK significantly elevat ed tissue levels of [H-3]-inositol phosphates in longitudinal muscle s lices preincubated with [H-3]-myo-inositol. The agonists potencies of BK, Lys-BK, Met-Lys-BK, Tyr5-BK and Tyr8-BK were in agreement with the ir relative potencies in the binding assay. The B1 receptor agonist de s-Arg9-BK, did not stimulate inositol phosphate production. The respon se to BK was blocked by known B2 receptor antagonists but not by the B 1 antagonist des-Arg9, Leu8-BK. 4 BK-induced phosphoinositide hydrolys is was unaffected by exposure of muscle slices to either atropine or i ndomethacin. 5 The results indicate that the B2 receptors linked to ph osphoinositide turnover in ileal longitudinal muscle exhibit propertie s similar to those involved in contractile responses. Also, the recept or mediating the phosphoinositide response is likely to be that labell ed in the [H-3]-BK binding studies.