ANALYSIS OF THE NEGATIVE INOTROPIC ACTION OF SOMATOSTATIN

Somatostatin (SS) was evaluated as a chronotropic and inotropic agent in isolated spontaneously beating auricles of rats, rabbits and guinea‐pigs. SS was completely inactive in rat and rabbit auricles but exerted a dose‐dependent, negative inotropic effect in guinea‐pig auricles in concentrations between 1.5 × 10−8 to 1.2 × 10−6 m. The negative inotropic effect of SS (6.0 × 10−8 and 3.0 × 10−7 m) was not inhibited by a mixture of antagonists containing practolol (7.9 × 10−6 m), phentolamine (3.5 × 10−7 m), methysergide (2.8 × 10−7 m), diphenhydramine (3.9 × 10−5 m), cimetidine (4.0 × 10−5 m) atropine (3.4 × 10−7 m) and indomethacin (1.4 × 10−5 m). The negative inotropic effect of SS was greatly potentiated by reduction in the Ca2+ concentration of the medium from 5.0 to 1.25 mm. On a molar basis, SS was equipotent with acetylcholine (ACh) as a negative inotropic agent in the guinea‐pig auricles. SS (6.0 × 10−8 and 6.0 × 10−7 m) was found to inhibit selectively the positive inotropic action of neurotensin (NT) in guinea‐pig but not in rat auricles. The inhibitory action of SS against NT was independent of its negative inotropic action. These results suggest that SS produces its negative inotropic action by interacting with specific receptors presumably located in the cell membrane of guinea‐pig atria. The interaction between SS and its receptor may cause a decreased Ca2+ diffusion and/or transport into the atrial cells. The physiological and pharmacological significance of these results is discussed. 1979 British Pharmacological Society