Evidence for neuro‐effector transmission through postjunctional α 2 ‐adrenoceptors in human saphenous vein

Self Cite

1 We have examined the effects of antagonists on the isometric contraction of the human saphenous vein produced by 5-hydroxytryptamine (5-HT).2 The 5-HT2-antagonist ketanserin (1 gM) had little effect on the lower part of the concentrationresponse curve to 5-HT, but markedly shifted the upper part of the curve. 3 Yohimbine caused an approximately parallel shift of the concentration-response curve to 5-HT, with a pA2 of 5.48, much lower than its pA2 against noradrenaline in the absence (6.36) or presence (7.06) of cocaine. 4 It is concluded that there are two components to the contractile response to 5-HT in human saphenous vein: at low concentrations 5-HT activates a yohimbine-sensitive receptor, and at higher concentrations 5-HT activates a 5-HT2-receptor.

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

An examination of 5‐hydroxytryptamine receptors in human saphenous vein

Docherty

Hyland

1986

Self Cite

“…In conclusion, the most striking finding of this study was that a2-adrenoceptors play a major role in mediating the vasoconstrictor responses to m-agonists and nerve stimulation, whereas in previous in vitro studies these responses were predominantly mediated by a,-adrenoceptors (Ferrell & Khoshbaten, 1989;1990a Docherty, 1989 (Docherty & Hyland, 1985). It could be argued that the difference in the results obtained in the in vitro and in vivo preparations may be related to different methodologies.…”

Section: Discussionmentioning

confidence: 48%

Sympathetic innervation and α‐adrenoceptor profile of blood vessels in the posterior region of the rabbit knee joint

Najafipour

Ferrell

1993

1 Experiments were performed to determine the nature of adrenoceptors mediating neurally-induced vasoconstriction of blood vessels in the posterior region of the rabbit knee joint capsule. 2 Electrical stimulation of the posterior articular nerve resulted in frequency-dependent vasoconstriction which was maximal at 10 Hz. This response was mediated predominantly by a2-adrenoceptors as it was only slightly reduced by prazosin administration and was not only abolished but converted into a dilator response by the a2-adrenoceptor antagonist rauwolscine. Further experiments with another specific al-adrenoceptor antagonist YM-12617 showed that the frequency-response curve in the presence of this antagonist did not differ significantly from control. 3 Neurally-induced vasoconstriction did not appear to have a purinergic component as it was unaffected by the P2x-purinoceptor desensitiser a, methylene ATP. 4 The rank-order of potency of a-adrenoceptor agonists given as a bolus by close intra-arterial injection was: adrenaline = UK-14304 > clonidine> phenylephrine, suggesting that the vasoconstrictor effects were mediated predominantly by postjunctional a2-adrenoceptors. 5 The M2-adrenoceptor antagonist rauwolscine converted the constrictor response to close intra-arterial injection of adrenaline into a dilator response. The vasoconstrictor responses to UK-14304, clonidine and phenylephrine were substantially inhibited by rauwolscine. The a,-adrenoceptor antagonist prazosin failed to inhibit the vasoconstrictor responses to adrenaline, clonidine and UK-14304 and resulted in enhancement of their constrictor effects. 6 The enhancement of the responses to the a, and a2 agonists by prazosin appeared to be specifically related to this agent as administration of YM-12617 did not show such enhancement. The dose-response curves to both clonidine and UK-14304 in the presence of YM-12617 did not differ significantly from control responses. Responses to phenylephrine were significantly reduced by YM-12617, indicating the presence of post-junctional a,-adrenoceptors. 7 These results show almost complete reversal of the adrenoceptor profile compared to results obtained in an earlier in vitro study, where responses were mediated predominantly by ax,-adrenoceptors with a small population of postjunctional a2-adrenoceptors (Ferrell & Khoshbaten, 1989). This suggests that the differing environment in vitro may not completely reflect the conditions prevailing in vivo.

“…Contractions to noradrenaline and nerve stimulationevoked contractions in the human saphenous vein are mediated predominantly by X2-adrenoceptors based both on the absolute and relative potencies of yohimbine and prazosin (Muller-Schweinitzer, 1984;Steen et al, 1984;Docherty & Hyland, 1985;Docherty, 1987 (Bylund, 1985;, this might suggest that all the a2-adrenoceptors examined in this study resemble the CA2A, based on absolute potency of prazosin. However, when potency of prazosin is expressed relative to yohimbine, prazosin is 20 (rat vas deferens), 9 (human saphenous vein) or 8 (rat atrium) times less potent than yohimbine in our functional studies, similar to the potency ratio found by Bylund for the a2B subtype as in neonatal rat lung or for the a2c subtype as in the OK cell line (Murphy & Bylund, 1988) with high affinity for prazosin (5-7.6nM), but prazosin was 260 times less potent than yohimbine at the a2A of human platelet (present data and Bylund, 1988).…”

Section: Discussionmentioning

confidence: 73%

No evidence for differences between pre‐ and postjunctional α₂‐adrenoceptors in the periphery

Connaughton

Docherty

1990

1 We have compared prejunctional x2-adrenoceptors in rat and guinea-pig vas deferens and rat and guinea-pig atria with postjunctional a2-adrenoceptors in human saphenous vein and human platelets employing the antagonists yohimbine and SK&F 104078 and other a2-adrenoceptor antagonists. 2 Yohimbine was approximately 10 times more potent prejuunctionally than SK&F 104078 at antagonizing the inhibition by the x2-adrenoceptor agonist xylazine of stimulation-evoked contractions in rat and guinea-pig vas deferens, and at increasing stimulation-evoked release of tritium in rat and guinea-pig atria pre-incubated with [3H]-noradrenaline. 3 Yohimbine was approximately 10 times more potent postjunctionally than SK&F 104078 at antagonizing contractions to noradrenaline in human saphenous vein and at displacing [3H]-yohimbine binding in human platelet membranes. 4 For the antagonists yohimbine, SK&F 104078, prazosin, phentolamine, CH 38083 and urapidil, there was a significant correlation between prejunctional potency in rat vas deferens atrium and postjunctional potency in human platelet, although the correlation was improved by the omission of prazosin. 5 We have no evidence for differences between functional pre-and postjunctional ac2-adrenoceptors in the periphery, although these functional receptors may differ from the ligand binding site in the human platelet.