Evidence against serotonin as a vasoconstrictor neurotransmitter in the rabbit basilar artery

It has been suggested recently that serotonergic nerves distinct from the known adrenergic innervation are present in cerebral blood vessels. We have confirmed that serotonin is present in the wall of rabbit cerebral arteries using a high-performance liquid chromatography technique, with levels in the basilar artery of 0.27 +/- 0.04 microgram/g wet wt. Furthermore, adrenergic denervation in vitro with 6-hydroxydopamine, while substantially reducing norepinephrine content, did not alter serotonin levels in the basilar artery. However, it was not possible to demonstrate specific accumulation of [3H]serotonin into distinct serotonergic nerves. Both the basilar artery and ear artery (which has been shown not to be innervated with serotonergic nerves) accumulated [3H]serotonin when incubated with a low concentration (10(-8) M). However, [3H]serotonin accumulation was reduced markedly in 6-hydroxydopamine-treated vessels as well as in the presence of the norepinephrine uptake blocker, desmethylimipramine. Furthermore, pretreatment with the serotonin uptake blocker, fluoxetine, did not inhibit selectively [3H]serotonin accumulation in the basilar artery. Thus, the majority of [3H]serotonin accumulation can be attributed to adrenergic nerves. The possibility that serotonergic nerves contribute to the neurogenic constrictor response of the rabbit basilar artery was also tested. Adrenergic denervation with 6-hydroxydopamine in vitro abolished the constrictor response to transmural nerve stimulation completely, but levels of endogenous serotonin were not affected. Thus, although the presence of endogenous serotonin in cerebral arteries has been confirmed, this substance does not appear to contribute to the neurogenic vasoconstriction seen in this vessel.