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- Chang, J Y, et al.
(författare)
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Cerebrovascular serotonergic receptors mediating vasoconstriction: further evidence for the existence of 5-HT2 receptors in rat and 5-HT1-like receptors in guinea-pig basilar arteries
- 1989
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 136:1, s. 59-67
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological experiments were carried out on isolated basilar arteries (BA) from the brain vasculature of guinea-pig and rat in order to characterize post-junctional serotonergic receptors mediating contraction by the use of selective agonists and antagonists. The sensitivity to 5-HT was higher, but the intrinsic activity lower, in guinea-pig compared to rat vessels. The contractile potency of the 5-HT1 agonists, 5-carboxamidotryptamine (5-CT), was three times higher than 5-HT in guinea-pig but 16 times lower in rat BA. In arteries from both species the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), only caused weak contraction. In rat BA, where the serotonergic contractile receptors are ketanserin-sensitive, mesulergine inhibited the contraction in doses high enough to block 5-HT2 receptors, and also propranolol slightly inhibited the contraction, probably due to its binding to these receptors. Methiothepin, a potent antagonist of the 5-HT1-like receptors, affected the contraction in a non-competitive manner. The antagonist profile was different in guinea-pig BA: propranolol was ineffective, mesulergine caused a slight, non-surmountable inhibition, whereas methiothepin acted as a true, competitive antagonist. The data support previous suggestions that the serotonergic contraction in rat BA is mediated by 5-HT2 receptors, whereas the present data show that 5-HT1-like receptors predominate in guinea-pig BA.
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| 2. |
- Chang, J Y, et al.
(författare)
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Serotonin potentiates noradrenaline-induced vasoconstriction through 5-HT1-type receptors in guinea pig basilar artery
- 1989
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 1559-7016. ; 9:5, s. 713-716
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Tidskriftsartikel (refereegranskat)abstract
- Based on the previous finding that 5-hydroxytryptamine (5-HT) co-exists with norepinephrine (NE) in cerebrovascular sympathetic nerve fibers and can be released during electrical nerve stimulation, the postjunctional interaction between the two amines was studied in isolated basilar artery of guinea pig. A low concentration of 5-HT, which in itself has little or no constrictive effect, potentiated the weak contraction of NE by almost 300%. The amplification was antagonized by methiothepin, but not by ketanserin, and it could be mimicked by methysergide. The marked potentiation is thus probably associated with the 5-HT1-like receptors, which earlier have been found to mediate the direct vasoconstrictive action of 5-HT in this vessel preparation.
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| 3. |
- Hardebo, Jan Erik, et al.
(författare)
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Characterization of the contractile and dilatory responses to electrical field stimulation in guinea-pig and monkey isolated pial arteries
- 1989
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Ingår i: Archives internationales de pharmacodynamie et de therapie. - 0301-4533. ; 300, s. 94-106
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Tidskriftsartikel (refereegranskat)abstract
- Changes in vascular tone brought about by electrical field stimulation were studied in isolated guinea-pig and monkey pial arteries, using stimulus intensities similar to, or weaker than, those usually utilized by other investigators. In the guinea-pig, excitation of the smooth muscle cells was easily induced, even at low intensity stimulus parameters. This contraction faded upon repeated stimulation. Certain characteristics indicated that the response was neurogenic with excitation of perivascular sympathetic nerve terminals, despite the fact that it persisted after treatment with guanethidine and phentolamine and was only little reduced by tetrodotoxin; surgical sympathectomy or pretreatment with reserpine abolished the response, whereas removal of endothelium or mast cell degranulation was without effect. Attempts were made to further characterize the substance released. It was probably not noradrenaline, neuropeptide Y, adenosine triphosphate, serotonin, histamine or acetylcholine. In the monkey, similar low intensity stimulus parameters induced a fully tetrodotoxin-sensitive contractile response, attributable to the release of noradrenaline alone. By a minor increase in stimulus intensity, tetrodotoxin-resistant contractions, probably due to direct smooth muscle activation, could easily be obtained in pial arteries from both species. Tests were also performed to elucidate whether a dilatation, caused by a neurogenic transmitter release, could be obtained in these vessels. In both species, however, only a tetrodotoxin-resistant response was found, even at weak stimulus intensities, in agreement with previous observations in vessels from several other species. The present data illustrate the need for a careful choice of stimulus parameters when vascular tonic responses upon electrical field stimulation are used as an index for neurogenic release. They also demonstrate that such a response may, indeed, be neurogenic despite marked resistance to tetrodotoxin.
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