SEROTONIN ANTAGONISM IN ISOLATED CANINE CEREBRAL ARTERIES

Abstract

In helically-cut strips of canine cerebral arteries, the dose-response curve of serotonin was not influenced by 10-7 M phentolamine but was slightly moved to the right and downward at 10-6 M. The contractile response to serotonin was unaffected by cocaine (3 .times. 10-6 M), atropine (10-6 M) and propranolol (10-6 M). The addition of LSD, ergotamine and methysergide caused a dose-dependent contraction. Treatment with LSD (10-9( and 10-8 M), ergotamine (10-10 to 10-8 M) and methysergide (10-8 to 10-6 M) shifted the dose-response curve of serotonin to the right and downward in a dose-dependent manner. The inhibitory effect of methysergide was reversed by washing, while that of ergotamine was not reversed. Apparent pA2 [Scale for measuring drug antagonism, (effective) concentration of agonist to antagonist] values of LSD, ergotamine and methysergide were 9.17, 9.63 and 7.92, respectively. Contractile responses to 20 mM K+ were not significantly influenced by these blocking agents even in the highest concentrations used. An .alpha.-adrenergic mechanism is not involved in the genesis of serotonin-induced contractions and serotonin acts directly on serotonergic receptors in canine cerebral arteries.