Kinins contribute to the contractile effects of rat glandular kallikrein on the isolated rat uterus.

Glandular kallikrein is known to promote contractions of the isolated, estrogenized rat uterus, perhaps independently of kinin formation. The recent availability of kinin receptor antagonists led us to study whether they might affect the oxytocic activity of kallikrein. DArg0-Hyp3-Thi5,8-DPhe7-bradykinin (8.5 x 10(-7) M) displaced the dose-response curves to both bradykinin (from 1.0 x 10(-9) to 4.0 x 10(-6) M) and kallikrein (from 4.7 x 10(-11) to 8.0 x 10(-9) M) approximately one order of magnitude to the right. This inhibition could not be due to a nonspecific effect on the uterine muscle, as the contractile response to oxytocin was not altered. In addition, carboxypeptidase B (a potent kininase) and kinin antibodies reduced the contractile response to kallikrein by 70 and 60%, respectively. Removal of the intervening agent restored the normal response. The effect of kallikrein depended on its enzymatic activity, inasmuch as kallikrein inactivated with D-Phe-Arg-Arg-CH2Cl was not oxytocic. Prolonged or multiple exposures to kallikrein completely abolished uterine response, whereas the effect of bradykinin was unaltered. Uterine horns rendered insensitive to kallikrein by prolonged exposure still contracted in response to trypsin. Kininogen was present in the uterine tissue in a concentration of 1.5 +/- 0.3 ng of bradykinin equivalents per mg wet wt. No more than 15.9 +/- 1.2% of this total was due to plasma contamination. Only 21.5 +/- 2.9% of total kininogen could be cleaved by kallikrein. We conclude that part of the oxytocic activity of kallikrein is related to generation of kinins from a kallikrein-sensitive kininogen present in the isolated rat uterus.(ABSTRACT TRUNCATED AT 250 WORDS)

A role for the kallikrein-kinin system in the regulation of osmotic water permeability in the toad bladder.

Captopril (CA), a specific inhibitor of kininase II, did not alter osmotic water permeability (Posm) when present in the mucosal bath of the urinary bladder isolated from the toad Bufo arenarum at a concentration of 2.3 X 10(-3) M. This treatment, however, caused a 65% enhancement in the increase in Posm following serosal exposure to vasopressin, oxytocin or theophylline, agents that increase intracellular cyclic AMP levels. The effect of captopril was prevented by procedures that reduce the kallikrein (KK)-like alkaline esterase activity present in the bladder (such as simultaneous exposure to 2.3 X 10(-5) M aprotinin, or pretreatment of the toads with 0.1 N NaCl for several days before the experiment) or by replacing the mucosal bath with fresh solution of identical composition after exposure to captopril. In contrast, changing the serosal bath did not alter the effect of the drug. These results are consistent with an effect of CA at a step beyond cAMP generation, and suggest it is mediated by release of a soluble factor, probably a kinin, into the mucosal bath. These observations, together with data previously published, suggest that the KK-kinin system may participate in the control of epithelial water and electrolyte permeability in the toad bladder. In particular, under environmental stress, it may become important in the regulation of the animal's extracellular fluid volume, thus exhibiting an adaptive value.