α1-Adrenoceptor subtypes and two receptor systems in vascular tissues

Muramatsu, Ikunobu; Murata, Satoshi; Isaka, Mitsuyoshi; Piao, Hailan; Zhu, Jun; Suzuki, Fumiko; Miyamoto, Sayako; Oshita, Masafumi; Watanabe, Yoshinari; Taniguchi, Tadatsugu

doi:10.1016/s0024-3205(98)00090-3

Cited by 40 publications

(31 citation statements)

References 7 publications

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“…In this regard, it is interesting to note that the alpha-1D AR subtype is highly sensitive to catecholamines and phenylephrine as compared with the alpha-1A and alpha-1B AR subtypes (Lomasney et al, 1991;Buckner et al, 1996;Graham et al, 1996). Additionally, the pEC 50 value (7.170.1) for phenylephrine in the reserpine-treated tail artery was the same as the pEC 50 value (7.270.1) in the thoracic aorta, where the adrenergic responses to phenylephrine have been known to be mainly mediated through alpha-1D ARs, irrespective of reserpine treatment (present study; Buckner et al, 1996;Muramatsu et al, 1998;Murata et al, 1999;Daly et al, 2002).…”

Section: Discussionsupporting

confidence: 60%

“…From these data, together with the high affinity of the alpha-1D AR subtype for catecholamines, it is possible that most of the alpha-1D AR subtype is sequestered or downregulated under sympathetically innervated conditions and that this process may be reversed by sympathetic denervation, resulting in an upregulation of the alpha-1D AR. It is also interesting to note in this regard, that the alpha-1D AR subtype can be readily detected in both functional and ligandbinding studies using the rat thoracic aorta (Buckner et al, 1996;Muramatsu et al, 1998;Tanaka et al, 2004). Importantly, this tissue is not sympathetically innervated (Table 1 in the present study; Berkowitz et al, 1971;Stassen et al, 1998).…”

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

confidence: 50%

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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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Section: Discussionsupporting

confidence: 60%

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

confidence: 50%

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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“…The selectivity was evaluated with two parameters: binding affinity to recombinant human a 1a-, a1b-and a1d-adrenoceptors expressed in Chinese hamster ovary (CHO) cells and functional affinity to native a1A-(rat caudal artery) (17), a 1B-(dog carotid artery) (18,19) and a 1D-(rat thoracic aorta) (20) adrenoceptors. A good relationship was already reported for a 1-adrenoceptorselective drugs between the recombinant and native a1-adrenoceptors (7,21).…”

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confidence: 60%

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes

Yoshio

Taniguchi

Itoh

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-Binding affinities of serotonin (5-HT)-receptor antagonists and agonists at human recombinant a1-adrenoceptor subtypes (a 1a-, a1b-and a1d-subtypes) were examined and compared with the functional affinities obtained in rat caudal artery (a1A-subtype), dog carotid artery (a1B-subtype) and rat thoracic aorta (=1D-subtype). Most of the 5-HT-receptor antagonists and agonists tested showed relatively high affinity to three a 1-adrenoceptor subtypes. The highest affinity close to 1 nM was seen for in binding and functional studies. 5-Methylurapidil (5-HT1A agonist) and BMY7378 (5-HT1A agonist) showed, respectively, a 1a(a 1A)-or a1d(a1D)-subtype selectivity in both binding and functional affinities, but spiperone (5-HT2A antagonist) showed a1b-selectivity only in binding affinity. Functional affinity of ritanserin (5-HT2A antagonist) to the a1B-subtype was approximately 500-fold lower than that of affinity to the =1b-subtype. The present results show that many 5-HT-receptor antagonists and agonists have high affinity to a1-adrenoceptors, but suggest that there is deviation between their functional affinities and binding affinities for some drugs.Keywords: Serotonin receptor antagonist, Serotonin receptor agonist, a 1-Adrenoceptor, Selectivity a1-Adrenoceptors comprise a heterogeneous family (1 -3). Molecular biological studies have provided evidence for the existence of at least three genes encoding a1a-, a1b-and a1d-adrenoceptors (with lowercase letters) that correspond to the pharmacologically defined native a1A-, a1B-and a 1D-adrenoceptors (with uppercase letters) (4, 5). Pharmacological studies have revealed several subtypeselective agents: for example, 5-methylurapidil, KMD-3213, RS-17053 and nigludipine for the a1a-subtype (6 -9); spiperone for the a1b-subtype (10); and BMY7378 for the a1d-subtype (11, 12). Among them, 5-methylurapidil, spiperone and BMY7378 were originally categorized in serotonin (5-HT) receptor agonists and / or antagonists.Many 5-HT receptor antagonists have been developed and some of them are now clinically used as anticoagulants, antihypertensive drugs and antipsychotic drugs (13,14). Such therapeutic diversity of 5-HT antagonists may be related to their wide spectrum for not only 5-HT receptor family but also for heterogeneous receptors such as dopamine receptors and a1-adrenoceptors (15, 16).The present study was undertaken to examine the possible selectivity for a1-adrenoceptor subtypes of 5-HT receptor agonists and antagonists including clinically active antipsychotic drugs. The selectivity was evaluated with two parameters: binding affinity to recombinant human a 1a-, a1b-and a1d-adrenoceptors expressed in Chinese hamster ovary (CHO) cells and functional affinity to native a1A-(rat caudal artery) (17), a 1B-(dog carotid artery) (18,19) and a 1D-(rat thoracic aorta) (20) adrenoceptors. A good relationship was already reported for a 1-adrenoceptorselective drugs between the recombinant and native a1-adrenoceptors (7, 21). MATERIALS AND METHODS Membrane preparation and radiolig...

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“…However, some differences were observed for the inhibitory actions on both the responses caused by both agonists. (Oshita et al, 1993;Muramatsu et al, 1998a). At 100 nM, prazosin produced a parallel rightward shift of the concentration-response curve for noradrenaline (Fig.…”

Section: Resultsmentioning

confidence: 81%

“…BMY 7378 [(8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro [4,5]decane-7,9-dione dihydrochloride] is an ␣-1D-selective antagonist (Goetz et al, 1995). In addition to these three ␣-1AR subtypes (A, B, and D), the presence of another ␣-1 AR subtype (the putative ␣-1L AR) has been identified using functional studies that reveal a unique pharmacological profile: low affinity for prazosin, RS-17053, and 5-methylurapidil but high affinity for KMD-3213 and tamsulosin (Muramatsu et al, 1995a(Muramatsu et al, , 1998aFord et al, 1996;Murata et al, 1999). However, the corresponding gene for the ␣-1L AR has not yet been identified.…”

mentioning

confidence: 99%

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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α1-Adrenoceptor subtypes and two receptor systems in vascular tissues

Cited by 40 publications

References 7 publications

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

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

Affinity of Serotonin Receptor Antagonists and Agonists to Recombinant and Native α1-Adrenoceptor Subtypes

Identification of α-1L Adrenoceptor in Rabbit Ear Artery

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