Nerves containing serotonin, its interaction with noradrenaline, and characterization of serotonin receptors in cerebral arteries of monkey.

Abstract

1 Immunohistochemistry was applied to study the presence of 5-hydroxytryptamine (5-HT) and dopamine-beta-hydroxylase (DBH) in cerebrovascular nerves of monkeys, and serotonergic receptors were characterized in the vessels by in vitro pharmacology. 2 A well-developed plexus of 5-HT immunoreactive fibres was found to supply the pial arteries at the base of the brain. The network closely resembled the distribution of neural DBH, used as an index for noradrenergic nerves. 3 5-HT contracted the basilar artery (BA) and middle cerebral artery (MCA) with equal potency and intrinsic activity. The effect was not antagonized by phentolamine or propranolol. 4 The 5-HT2 receptor antagonist, ketanserin, inhibited the response to 5-HT in a competitive manner in both vessels, with pA2 values obtained from Schild plots of 9.15 in BA and 9.40 in MCA. 5 Electrical field stimulation elicited a neurogenic contraction that was completely blocked by 3 X 10(-7) M tetrodotoxin, 3 X 10(-6) M guanethidine, and 10(-6) M phentolamine. The response was also antagonized by ketanserin, but only in concentrations higher than those inhibiting the response to 5-HT. 6 In accordance with the findings during nerve stimulation, noradrenaline (NA) contracted the pial arteries, particularly MCA where the intrinsic activity closely resembled the value obtained with 5-HT. Ketanserin antagonized the response, but less efficiently than that induced by 5-HT. 7 5-HT had no effect on the (noradrenergic) neurogenic contraction obtained during electrical stimulation. Nor did 5-HT affect the contraction induced by exogenous NA. 8 It is concluded that 5-HT and NA may be co-localized in perivascular nerves of the monkey brain. 5-HT contracts pial arteries through postjunctional 5-HT2 receptors, but does not seem to interfere prejunctionally with the noradrenergic nerves or with exogenous NA.