Functional 5-HT receptor subtypes in the isolated canine common carotid artery

Abstract

The vascular responses to 5-hydroxytrypamine (5-HT), 5-carboxamidotryptamine (5-CT, a selective 5-HT1-like receptor agonist), alpha-methyl-5-HT (alpha-M-5-HT, a relatively selective 5-HT2 receptor agonist), noradrenaline (NA), and KCl were examined in isolated, cannulated, and perfused canine common carotid arterial preparations. They caused strong vasoconstrictions. The rank order of vasoconstrictive potency was 5-HT > alpha-M-5-HT > or = NA > 5-CT >> KCl. The 5-HT-induced vasoconstriction was significantly depressed by methysergide (a 5-HT1 and 5-HT2 receptor antagonist), ketanserin (a selective 5-HT2 receptor antagonist), and spiperone (a selective 5-HT2 receptor antagonist). The 5-CT- and alpha-M-5-HT-induced vasoconstrictions were also significantly inhibited by methysergide, spiperone, and ketanserin. The NA-induced vasoconstriction was readily inhibited by bunazosin (an alpha-adrenoceptor antagonist) and ketanserin but not significantly inhibited by spiperone and methysergide. KCl has a weak potency for producing a vasoconstriction of the canine common carotid artery. A relatively large dose of diltiazem (a calcium channel-blocker) did not modify 5-HT-induced vasoconstrictions.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of 5‐HT1B receptors in collar‐induced hypersensitivity to 5‐hydroxytryptamine of the rabbit carotid artery

“…Spiperone (1, 10 and 100 n M ) and methysergide (1, 10 and 100 n M ), both predominantly 5‐HT 2A receptor antagonists ( Feniuk et al ., 1985 ; Vhora & Chiba, 1994 ), decreased dose‐dependently the sensitivity to serotonin, but did not influence the maximal response reached. They acted as competitive, surmountable antagonists in sham and collared rings (Table 2).…”

Collar‐induced elevation of mRNA and functional activity of 5‐HT1B receptor in the rabbit carotid artery

“…Yet, the maximum response to 5‐HT was increased but did not reach statistical significance (Table 1). In the absence of the pre‐contractile agent KCl, the 5‐HT 2A antagonist spiperone (0.1 μ M ) ( Vhora & Chiba, 1994 ) induced a parallel rightward shift (123 fold) of the 5‐HT concentration response curves in sham rings without changing the maximum response or the Hill slope of the curve (Table 1, Figure 1). This is in agreement with the competitive and surmountable antagonism exerted by spiperone in the rabbit carotid artery ( Geerts et al ., 1999 ).…”

“…This pre‐stimulation will be mentioned as pre‐contractile status throughout the text. Subsequently, the two CRC's to 5‐HT (with and without pre‐contraction) were repeated in the presence of a 5‐HT 2A receptor antagonist, either spiperone (0.1 μ M ) ( Feniuk et al ., 1985 ; Vhora & Chiba, 1994 ) or ketanserin (0.1 μ M ) ( Conolan et al ., 1986 ; Van Nueten et al ., 1986 ), added 30 min prior to the organ bath. In each experiment one sham and one collared ring did not receive the antagonist or the pre‐contractile agent to allow for correction of time effects.…”

Inhibition of Intracellular Calcium Elevation and Blunting of Vasopressor Response due to Serotonin by Ginkgolide B

“…Transient intracellular Ca 2+ is an essential signaling system to regulate vascular constriction [8]. Serotoin selectively activates the 5-HT 2 receptor in vascular smooth muscle [9] that results in cytoplasmic Ca 2+ release, while a high concentration of potassium stimulates extracellular Ca 2+ influx through membrane voltage-dependent Ca 2+ channels. It was recently reported that WEB 2086, another PAF antagonist compound, effectively inhibited intracellular Ca 2+ elevation caused by PAF in smc [10].…”