Effects of tertatolol on post- and prejunctional beta adrenoceptors.

The effects of tertatolol, a new and powerful beta adrenoceptor blocking drug, on post- and prejunctional beta receptors were investigated; canine vascular tissues (saphenous veins, coronary arteries and splenic arteries) and guinea-pig trachea and atria were used. At concentrations below 10(-5) M, tertatolol did not alter basal tension or contractile responses to electrical stimulation, norepinephrine, K+ or prostaglandin F2 alpha; at doses at or above 10(-5) M the drug-evoked contractions which were reduced by phentolamine and were absent in denervated veins. Tertatolol at 10(-5) M and 3 X 10(-5) M augmented the basal efflux of [3H] norepinephrine in saphenous veins labeled with the 3H-transmitter. In veins, 10(-5) M of tertatolol depressed the contractions caused by electrical stimulation without affecting those to exogenous norepinephrine; this concentration of the drug also inhibited the stimulation-induced overflow of [3H]norepinephrine. The major part of the present study was designed to test the beta receptor blocking properties of tertatolol and to compare its effects with those of propranolol. Tertatolol inhibited, in a concentration-dependent manner, the relaxations caused by isoproterenol in saphenous veins, splenic arteries and coronary arteries and the relaxations evoked by norepinephrine and epinephrine in coronary arteries; the potency of tertatolol was higher than that of propranolol. In trachea and right atria of the guinea-pig, tertatolol inhibited, in a concentration-dependent manner, the dose-response curves to isoproterenol; the relative potency of tertatolol was higher than that of propranolol. In dog saphenous veins, previously incubated with [3H]norepinephrine, tertatolol (10(-7)M) blocked the increased stimulation-evoked overflow of the 3H-transmitter induced by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Release of chromaffin granular content on interaction with plasma membranes.

Cell-free interaction between bovine adrenal medullary plasma membranes and chromaffin granules results in the release of the granular content, a process specifically controlled by micromolar concentrations of calcium and therefore regarded as a putative model for exocytosis. The density gradient distribution of interacted organelles (1 min at 37 degrees C) was compared with the distribution of noninteracted material (kept at 0 degree C). Self-generating Percoll gradients, in which intact chromaffin granules were separated from plasma membranes and empty granule "ghosts," were used. The plasma membrane-induced release of the chromaffin granular matrix upon concomitant incubation was demonstrated by the disappearance of the "intact granule" peak accompanied by a proportional rise of the "granule ghost" peak. The degree of granule disappearance depended on the amount of plasma membranes added. The soluble content of the fraction that had disappeared was dispersed throughout the gradient. No shift of the granule peak toward intermediate densities was observed; this suggests that the loss of each granule's content is an all-or-none phenomenon rather than a partial release.