Cardiac actions and structural--activity relationship of parathyroid hormone on isolated frog atrium

The hypercalcemic and hypotensive actions of parathyroid hormones (PTH), parathyroid extract, and synthetic PTH-(1-34) have been reported in many different animals. However, their cardiac action was only recognized recently. In the present study, experiments were designed to examine (1) whether PTH possesses any cardiac action on the isolated frog atrium, and (2) the importance of methionine and arginine of bPTH-(1-34) in cardiac action. Six different bPTH analogs were tested in frog atria in vitro: bPTH-(1-34); H2O2-treated bPTH-(1-34); [Nle8, Nle18, Tyr34]-bPTH-(1-34); H2O2-treated [Nle8, Nle18, Tyr34]-bPTH-(1-34); arginine-modified bPTH-(1-34); and arginine-regenerated bPTH-(1-34) (Nle-norleucine). bPTH-(1-34) produced positive chronotropic and inotropic responses. Oxidation with hydrogen peroxide abolished both actions of bPTH-(1-34). [Nle8, Nle18, Tyr34]-bPTH-(1-34) also possesses this cardiac-stimulating property. The H2O2 treatment of this analog did not alter the chronotropic action, but a decrease in the inotropic action was observed. The arginine-modified bPTH-(1-34) was much less potent than its native hormone, while the reversal of the arginine modification partially restored the biopotency. From these data, it is concluded that (1) bPTH-(1-34) possesses both positive chronotropic and inotropic effects on the frog atrium, (2) the cardiac actions of bPTH-(1-34) may be closely related with its hypotensive property, (3) methionines are not necessary for the cardiac actions, and (4) arginines are important for the cardiac-stimulating effects of bPTH.