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Catecholamine secretion in the perfused rat adrenal medulla stimulated by bradykinin was characterized. The mean adrenaline secretion rate over the first 4 min after exposure to 100 nM bradykinin was 280 pmol/min. The secretion decreased by desensitization to 40°/0 of the initial level within 20 min. The stimulant effect of bradykinin was removed by a l0-min washout but the desensitization persisted for longer periods. Although noradrenaline secretion was also evoked by bradykinin, it amounted to only 4% of the adrenaline secretion, which was markedly smaller as compared with 24% for acetylcholine (ACh)-evoked noradrenaline secretion. In a C8.2+-Cl6fICl6I'1l medium, the bradykinin-evoked catecholamine secretion was reduced by 49% of the control (2 mM Ca2+), whereas the ACh-evoked secretion by 87%. The bradykinin-evoked secretion was almost completely inhibited in l mM EGTA-containing, Ca”-free medium. The presence of a Ca“ channel blocker, methoxyverapamil (D600) (100 ;1M) did not affect the bradykinin-evoked secretion but inhibited the ACh-evoked secretion by 80%. These results suggest that bradykinin leads to the catecholamine secretion by a pathway different from that for ACh. Although bradykinin is known as a potent stimulant for adrenal medullary catecholamine secretion (2, l0, l5), the secretory response has not been characterized in detail. Accordingly, the mechanism of action of bradykinin resulting in the secretion remains unelucidated. In the present study, it is demonstrated that catecholamine secretion evoked by bradykinin is different from that evoked by acetylAbbrew'ar:'0ns: ACh, acetylcholine; D600, methoxyverapamil; EDTA, ethylenediaminetetraacetic acid; EGTA, ethylene glycol bis(,6’-aminoethyl ether)N,N,N’,N"-tetraacetic acid; HEPES, 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid; HPLC, high performance liquid chromatography choline in its requirement for extracellular calcium and in its sensitivity to a Ca channelblocking agent. MATERIALS AND METHODS Perfusion of the adrenal gland was carried out by a method similar to that described by Kidokoro and Ritchie (5). The left adrenal gland of male Wister rats (250-450 g) was cannulated under sodium pentobarbital anesthesia through the adrenal vein and perfused retrogradely with a standard medium (modified Krebs solution). The gland was then removed and stabilized by a 50-min perfusion with the standard medium before initiation of secretory stimulation. The solutions with which the adrenal gland was perfused at a rate of

<b>CHARACTERISTICS OF BRADYKININ-EVOKED SECRETORY RESPONSE IN THE PERFUSED RAT ADRENAL </b><b>MEDULLA </b>