Indoleaminergic mechanisms in brain vessels; Localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine

Abstract

Immunocytochemical studies have revealed the presence of 5-HT-containing [5-hydroxytryptamine] nerve fibers in all parts of the cerebrovascular bed (arteries, arterioles and veins) of mouse, rat, guinea-pig, rabbit and cat. Biochemical measurements (using HPLC [high performance liquid chromatography] revealed substantial concentrations of 5-HT and 5-HIAA [5-hydroxyindoleactic acid] in the pial vessels of the rat, rabbit, cat and man, the amounts corresponding well with the density of the perivascular nerve supply. The uptake of 3H-5-HT was studied in arteries removed from the circle of Willis in rats. Maximum uptake was reached after 15 min of incubation at 37.degree. C and plateaued at 30 min. The reaction was temperature-dependent and absent if performed at 0% C. Pharmacological experiments on isolated middle cerebral and basilar arteries showed that vessels from rat and dog were contracted by .apprx. 90% upon administration of 5-HT, whereas vessels from guinea-pig, rabbit, cat and man were contracted by 40-60% relative to 124 mM K+. The EC50 [median effective concentration] values in the different species varied by between 1.5 .times. 10-7 M (rat) and 3 .times. 10-9 M (dog). The 5-HT-induced contractions were blocked by the 5-HT antagonists, methysergide, methergoline and ketanserin. Transmural nerve stimulation (TNS) of the rabbit basilar artery revealed a tetrodotoxin sensitive constriction whereas TNS of cat and dog middle cerebral arteries caused a tetrodotoxin-sensitive relaxation. The relaxation was not significantly attenuated until high doses of methergoline (3 .times. 10-6 M) or ketanserin (3 .times. 10-5 M) had been given. The contraction obtained upon electrical field stimulation of the rabbit basilar artery was reduced by the 5-HT antagonists only in concentrations of 10-6 M and above.