1 In atrial preparations of the young guinea-pig (
body weight 150-250 g), five
proteolytic enzymes (
trypsin,
chymotrypsin, bacterial-Al-
proteinase (
nagarse),
bromelain and
kallikrein) produced concentration-dependent positive inotropic and chronotropic effects, while they exerted only minimal effects on the papillary muscle preparations. 2 To characterize the effects, further experiments were conducted in atrial preparations using
trypsin. There was a strong tendency for tachyphylaxis: a second exposure to the same concentration of
trypsin resulted in considerably smaller positive inotropic and chronotropic effects. The positive inotropic and chronotropic effects of this substance were not affected by
propranolol (5 X 10(-7)M). However, an accumulation of
cyclic AMP was observed and the positive inotropic and chronotropic effects were potentiated by
aminophylline (10(-4)M) in association with an augmentation of the accumulation of
cyclic AMP. In preparations partially depolarized with high K+ (22mM) medium (contractions ceased under this condition)
trypsin 100 micrograms ml-1 reinstated the contraction. Treatment of the preparation with
aprotinin (200 u ml-1) resulted in a strong inhibition of the positive inotropic and chronotropic effects. 3
Islet activating protein (IAP), a specific inhibitor of the 'inhibition specific'
guanine nucleotide binding regulatory
protein of the
adenylate cyclase system, did not produce significant inhibition of the positive inotropic and chronotropic effects of
trypsin, whereas it produced a complete inhibition of the negative inotropic and chronotropic effects of
carbachol. 4. These results suggest that the positive inotropic and chronotropic effects ofproteolytic
enzymes are intimately connected with the proteolytic activities through which
adenylate cyclase is activated to produce an accumulation of
cyclic AMP within the myocardium. The destruction of the 'inhibition specific'
guanine nucleotide regulatory
protein of the
adenylate cyclase was not substantiated as a mechanism of activation of the
adenylate cyclase.