Bradykinin stimulates electrogenic bicarbonate secretion by the guinea pig gallbladder

We studied bradykinin effects upon electrogenic ion transport across voltage-clamped guinea pig gallbladder, and found stimulation after both mucosal (EC50 = 0.2 microM) and serosal addition (EC50 = 10 microM). The mucosal effect is dose-dependent, reproducible and sustained. Responses to bradykinin were unaffected by amiloride (1 mM) or piretanide (1 mM) but were attenuated by acetazolamide (1 mM), indicating the charge-carrying ion species to be bicarbonate. This was confirmed by abolishing the short circuit current response to bradykinin with bicarbonate-free solutions. Tetrodotoxin (1 microM) did not alter the response, indicating that neurons are not involved. This effect of bradykinin on gallbladder bicarbonate transport appears to be dependent upon arachidonate metabolism because the cyclooxygenase inhibitor piroxicam reversibly abolished the effect. In addition, prostaglandin E2 was more effective (EC50 = 0.01 microM) than bradykinin in stimulating short circuit current. This newly appreciated ion transporting effect of bradykinin occurs in a tissue where kinin effects upon afferent nerve endings and smooth muscle are also evident and raise several questions about kinin involvement in stone formation or local inflammatory events.