Indoleaminergic mechanisms in brain vessels; localization, concentration, uptake and in vitro responses of 5-hydroxytryptamine.
Immunocytochemical studies have revealed the presence of 5-HT-containing nerve fibres in all parts of the cerebrovascular bed (arteries, arterioles and veins) of mouse, rat, guinea-pig, rabbit and cat. Biochemical measurements (using HPLC) revealed substantial concentrations of 5-HT and 5-HIAA 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 degrees C and plateaued at 30 min. The reaction was temperature-dependent and found to be absent if performed at 0 degrees C. Pharmacological experiments on isolated middle cerebral and basilar arteries showed that vessels from rat and dog were contracted by approximately 90% upon administration of 5-HT, whereas vessels from guinea-pig, rabbit, cat and man were contracted by 40 to 60% relative to 124 mM K+. The EC50 values in the different species varied by between 1.5 X 10(-7) M (rat) and 3 X 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 X 10(-6) M) or ketanserin (3 X 10(-5) M) had been given.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004558:Electric Stimulation; D006168:Guinea Pigs; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D007120:Immunochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009412:Nerve Fibers / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D012702:Serotonin Antagonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid