Is α1D-adrenoreptor protein detactable in rat tissues?

Yang, Ming; Verfürth, Frank; Büscher, Rainer; Michel, Martin C.

doi:10.1007/pl00004966

Cited by 84 publications

(51 citation statements)

References 31 publications

(61 reference statements)

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“…4A), and 5-methylurapidil. The proportions of high-and low-affinity sites were almost equal ( (Oshita et al, 1993;Yang et al, 1997) and in Krebs' incubation buffer, which was essentially identical with that used for intact tissue segment binding procedure. In both cases, […”

Section: Resultsmentioning

confidence: 77%

Identification of α-1L Adrenoceptor in Rabbit Ear Artery

Hiraizumi-Hiraoka

Tanaka²,

Yamamoto³

et al. 2004

J Pharmacol Exp Ther

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The ␣-1L adrenoceptor (AR) was identified in rabbit ear artery by both functional and ligand binding studies. In functional studies using arterial rings, the contractile response to NS-49 [(R)-(Ϫ)-3Ј-(2-amino-1-hydroxyethyl)-4Ј-fluoromethanesulfonanilide hydrochloride] (␣-1A and ␣-1L AR-selective agonist) was competitively antagonized with low affinities by prazosin, RS-17053 [N-[2-(2-cyclopropylmethoxyphenoxy) ethyl]-5-chloro-␣,␣-dimethyl-1H-indole-3-ethamine hydrochloride], and 5-methylurapidil but with high affinities by tamsulosin and KMD-3213In contrast, the response to noradrenaline (nonselective ␣-1 AR agonist) was inhibited noncompetitively by these antagonists (except 5-methylurapidil) with Schild slopes different from unity. These results suggest that the response to NS-49 was mediated predominantly via ␣-1L ARs, whereas the response to noradrenaline was produced through two distinct ␣-1 AR subtypes (presumably ␣-1B and ␣-1L ARs). In binding studies with intact segments of rabbit ear artery, [3 H]KMD-3213 bound with high affinity (pK D ϭ 9.7) to ␣-1 ARs, which were subdivided by prazosin, RS-17053, and 5-methylurapidil into two subtypes (␣-1A and ␣-1L ARs). In contrast, [3 H]prazosin binding sites in ear artery segments (pK D ϭ 9.8) were identified as ␣-1A and ␣-1B ARs. In conventional binding studies using isolated rabbit ear artery microsomal membranes, [ 3 H]KMD-3213 binding sites were identified as ␣-1A ARs with high affinities for prazosin, RS-17053, and 5-methylurapidil. Our study indicates that an ␣-1L AR having a unique pharmacological profile coexists with ␣-1A and ␣-1B ARs in rabbit ear artery and can be identified either functionally or by binding studies using intact tissues but not microsomal membrane preparations.

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Section: Resultsmentioning

confidence: 77%

Identification of α-1L Adrenoceptor in Rabbit Ear Artery

Hiraizumi-Hiraoka

Tanaka²,

Yamamoto³

et al. 2004

J Pharmacol Exp Ther

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“…However, in contrast with the aorta but like the tail artery, the endogenous noradrenaline level in the spleen was high and was markedly reduced by reserpine treatment. Present and previous functional or binding studies have clearly demonstrated the exclusive presence of alpha-1B AR subtype in rat spleen, irrespective of reserpine treatment (Kenakin & Novak, 1988;Yang et al, 1997;Buckner et al, 2002;Zhang et al, 2002). Thus, it does not appear that noradrenaline depletion and/or lack of adrenergic input necessarily cause the changes of alpha-1 AR expression and supersensitivity in sympathetically innervated tissues all.…”

Section: N Taki Et Al Alpha-1d Adrenoceptors In Supersensitivity 653mentioning

confidence: 66%

Alpha‐1D adrenoceptors are involved in reserpine‐induced supersensitivity of rat tail artery

Taki

Tanaka

Zhang

et al. 2004

British J Pharmacology

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1 We examined reserpine-induced chemical denervation supersensitivity with special reference to alpha-1 adrenoceptor (AR) subtypes. 2 Chronic treatment with reserpine for 2 weeks depleted noradrenaline in the tail artery and spleen of rats. Noradrenaline in the thoracic aorta was negligible before and after reserpine treatment. 3 The treatment with reserpine produced supersensitivity in the contractile responses of the rat tail artery to phenylephrine, 5-HT and KCl, resulting in leftward shift of concentration-response curves (11.6-, 2.5-and 1.1-fold at EC 50 value, respectively). These results suggest a predominant sensitization of the alpha-1 AR-mediated response by reserpine treatment. 4 BMY 7378 at a concentration (30 nM) specific for blocking the alpha-1D AR subtype, but not KMD-3213 at a concentration (10 nM) selective for blocking the alpha-1A AR subtype, inhibited the supersensitivity of the phenylephrine-induced response in the reserpine-treated artery. On the other hand, the response to phenylephrine in reserpine-untreated artery was selectively inhibited by the same concentration of KMD-3213, but not by BMY 7378. Prazosin, a subtype-nonselective antagonist, blocked the responses to phenylephrine with the same potency, regardless of reserpine treatment. 5 In the thoracic aorta and spleen, no supersensitivity was produced in the responses to phenylephrine by reserpine treatment. 6 In a tissue segment-binding study using [ 3 H]-prazosin, the total density and affinity of alpha-1 ARs in the rat tail artery were not changed by treatment with reserpine. However, alpha-1D AR with high affinity for BMY 7378 was significantly detected in reserpine-treated tail artery, in contrast to untreated artery. Decreases in alpha-1A AR with high affinity for KMD-3213 and alpha-1B AR with low affinities for KMD-3213 and BMY 7378 were also estimated in reserpine-treated tail artery. 7 Alpha-1D AR mRNA in rat tail artery increased to three-folds by reserpine treatment, whereas the levels of alpha-1A and 1B mRNAs were not significantly changed. 8 The present results suggest that chronic treatment with reserpine affects the expression of alpha-1 AR subtypes of rat tail artery and that the induction of alpha-1D ARs with high affinity for catecholamines is in part associated with reserpine-induced supersensitivity.

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“…It has been reported that methoxamine is a relatively selective a 1A-adrenoceptor agonist (9), and Minneman et al (10) reported that methoxamine is approximately 20-fold more potent to activate a1a-than a1b-and a1d-adrenoceptors in mediating [ 3 H]inositol phosphate formation. It was suggested that a1A-adrenoceptors might not be so abundant in the rat mesenteric artery (10,11). On the other hand, noradrenaline and phenylephrine show relative selectivity for the a 1d-adrenoceptor subtype (10, 11).…”

Section: Discussionmentioning

confidence: 99%

Existence of Functional α1A- and α1D- but No α1B-Adrenoceptor Subtypes in Rat Common Carotid Arteries

Chiba

Tsukada

2002

Japanese Journal of Pharmacology

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ABSTRACT-Using the cannula inserting method, vasoconstrictor responses to a1-adrenoceptor agonists (noradrenaline [NA], phenylephrine [PE] and methoxamine [ME]) and effects of a 1-adrenoceptor antagonists (WB4101, chloroethylclonidine [CEC] and BMY7378) were investigated in isolated and perfused rat common carotid arteries. The rank order of agonist potency and efficacy was NA = PE > ME. Either WB4101 or BYM7378 inhibited NA-and PE-induced constrictions in a dose-related manner. CEC did not inhibit the NA-and PE-induced responses. The ME-induced responses were also significantly blocked by either WB4101 or BMY7378. From these results, it is concluded that there are functional a 1A-and a1D-adrenoceptor subtypes in rat common carotid arteries, but no functional a1B subtype.Keywords: Cannula inserting method, Rat common carotid artery, a1-Adrenoceptor subtype Previously, in isolated rat common carotid arteries we investigated pharmacological features of vascular responses (1), using the cannula insertion technique (2, 3). It was demonstrated that noradrenaline and phenylephrine caused a long-lasting vasoconstriction (30 -60 min) even in a single injection of each compound, although other vasoconstrictor compounds (5-HT, PGF2=, angiotensin II or KCl) caused a relatively short-lasting constriction (within 20 min), indicating that this artery responded well to the a 1-adrenoceptor agonist. On the other hand, selective a2-adrenoceptor agonists, clonidine and xylazine, did not cause any vascular response in the same arterial preparation, indicating that there are no functional a2-adrenoceptors (1). Thus, it is interesting to clarify the a1-adrenoceptor subtypes in the rat common carotid artery. a1-Adrenoceptors are a heterogeneous family of G-protein coupled receptors. It is recognized that there are three functional a1-adrenoceptor subtypes, a1A, a1B and a1D, corresponding to the cloned subtypes, a 1a, a1b and a1d, respectively (4, 5). Recently, a selective a 1D-adrenoceptor antagonist, BMY7378, was introduced (6). Therefore, in the present study we investigated the postsynaptic a1-adrenoceptor subtypes of the isolated rat common carotid artery by using selective a1A-, a1B-and a1D-adrenoceptor subtype antagonists (WB4101, chloroethylclonidine and BMY7378, respectively). MATERIALS AND METHODSMale Wistar rats (weighing an average of 220 g, aged 7 weeks) were used in this study. After ether anesthesia and treatment with sodium heparin (200 units/ kg, i.v.), these animals were sacrificed by rapid exsanguination and then the common carotid artery was excised and immersed immediately in cold Ringer solution at 4°C. Isolated common carotid arteries that were 10 to 11 mm in length and 0.8 to 0.9 mm in outer diameter were selected for study. A stainless steel cannula with small holes 2 mm from the distal sealed end (25 gauge and 3 cm in length) was carefully inserted into each vessel segment to avoid injury of the intraluminal surface of the isolated vessel. Segments were set up in the bath for preparation as described by Tsu...

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Is α1D-adrenoreptor protein detactable in rat tissues?

Cited by 84 publications

References 31 publications

Identification of α-1L Adrenoceptor in Rabbit Ear Artery

Identification of α-1L Adrenoceptor in Rabbit Ear Artery

Alpha‐1D adrenoceptors are involved in reserpine‐induced supersensitivity of rat tail artery

Existence of Functional α1A- and α1D- but No α1B-Adrenoceptor Subtypes in Rat Common Carotid Arteries

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