Bradykinin stimulation of phosphoinositide hydrolysis in guinea‐pig ileum longitudinal muscle

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Abstract
Bradykinin (BK)‐induced contraction of ileal smooth muscle is assumed to be due to phosphoinositide hydrolysis but this has never been reported. We have investigated whether BK receptors are linked to this transduction mechanism in guinea‐pig ileum longitudinal muscle and determined whether these receptors are equivalent to those labelled in [3H]‐BK binding assays. In membranes prepared from longitudinal muscle, [3H]‐BK bound to a single class of sites with high affinity. Characterization of the binding with BK analogues indicated that the radioligand selectivity labelled a B2 type receptor. BK significantly elevated tissue levels of [3H]‐inositol phosphates in longitudinal muscle slices preincubated with [3H]‐myo‐inositol. The agonists potencies of BK, Lys‐BK, Met‐Lys‐BK, Tyr5‐BK and Tyr8‐BK were in agreement with their relative potencies in the binding assay. The B1 receptor agonist des‐Arg9‐BK, did not stimulate inositol phosphate production. The response to BK was blocked by known B2 receptor antagonists but not by the B1 antagonist des‐Arg9, Leu8‐BK. BK‐induced phosphoinositide hydrolysis was unaffected by exposure of muscle slices to either atropine or indomethacin. The results indicate that the B2 receptors linked to phosphoinositide turnover in ileal longitudinal muscle exhibit properties similar to those involved in contractile responses. Also, the receptor mediating the phosphoinositide response is likely to be that labelled in the [3H]‐BK binding studies.