Positive Chronotropic Effect of Dialysable Peptides Derived from Plasmin Digestion of Bovine Fibrinogen Preparations. Role of Cyclic AMP

Dialysable peptides (< 5,000 M. W.) derived from plasmin digestion of bovine fibrinogen preparations (Kabi) exerted a marked positive chronotropic effect on isolated rat atria. This effect reached a peak within two to four minutes, lasted as a plateau during four to six minutes and then slowly disappeared. It was abolished by glycolytic inhibitors such as NaF and 2-deoxy-D-glucose, not by inhibitors of oxidative phosphorylation such as 2,4-dinitrophenol. Ouabain, histamine and propranolol had no effect on the digests-induced chronotropic effect. Theophylline, an inhibitor of phosphodiesterases, showed an additive effect, whereas imidazole, an activator of phosphodiesterases, was inhibitory. Both cyclic AMP levels and phosphorylase activity of isolated rat atria were increased by the digests. The maximum increase was observed 30 and 90 seconds respectively, after the addition of the digests to the isolated atria. Theophylline exerted an additive effect and imidazole an inhibitory effect on digests-induced increase of cyclic AMP levels and phosphorylase activity. In our test system, digests behaved similarly to glucagon. It is concluded that cyclic AMP plays an important role in mediating the described positive chronotropic effect of fibrinogen-derived peptides. Such a role of cyclic AMP could also be relevant for other biological activities exerted by these peptides (e.g. the inhibition of ADP-induced platelet aggregation and the increase of vascular permeability and of the chemotactic activity of leucocytes).

(Supported by Grant N. 73.00400.04 of the Italian Research Council (C. N. R.).)

 

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