Cloning, Functional Expression and Tissue Distribution of Human cDNA for the α1C-Adrenergic Receptor

Hirasawa, Akira; Horie, Kuniko; Takano, Teruo; Takagaki, Kazuchika; Murai, Masatoshi; Yano, Junichi; Tsujimoto, Gozoh

doi:10.1006/bbrc.1993.2130

Cited by 154 publications

(100 citation statements)

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“…No consensus polyadenylation site was present in "400 bp of rat alc 3' UTR (Fig 1), nor is one present in --1000 bp of bovine 3' UTR20 or "300 bp of human 3' UTR. 21 The bovine alc also contains =750 bp of 5' UTR. 20 Thus, long UTRs can account at least for the 3-kb alc transcript and might also explain the 9.5 -and 11-kb transcripts (Fig 3), although the latter might also reflect incomplete mRNA processing.…”

Section: Northern Blot Analysismentioning

confidence: 99%

Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

Stewart

Rokosh

Bailey

et al. 1994

Circulation Research

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a,-Adrenergic receptor (AR) activation in cardiac muscle has several different physiological effects that might be mediated through different a,-AR subtypes. Two a,-AR subtypes have been cloned from the rat, the alB and the alD; both are present in adult rat heart. A third subtype, the a,c, cloned from the cow and human, was reported to be absent in the rat. However, we recently found alc mRNA in adult rat heart by using a partial alc cDNA. Thus, all three cloned a,-AR subtypes are present in the heart, but it is unknown whether each is expressed in cardiac myocytes or in cardiac fibroblasts.In the present study, the full-length rat alc-AR was cloned from cultured neonatal cardiac myocytes. alc mRNA transcripts of 3, 9.5, and 11 kb were present in adult rat heart by Northern blot analysis. alB-, alc-, and alD-subtype mRNAs were each present in isolated adult and neonatal cardiac I n cardiac muscle, a1-adrenergic receptor (AR) activation has several different physiological effects, including control of energy production,' increased and decreased inotropy and chronotropy,2-4 preconditioning against ischemic injury,5 reduction of myocardial stunning,6 and induction of cardiac myocyte hypertrophy and gene transcription.7-9 In addition, in the coronary arteries, a,-AR activation produces vasoconstriction.10"11 a,-ARs belong to the superfamily of G proteincoupled receptors with seven transmembrane domains. Like the other receptors for catecholamines -,-AR, a2-AR, and dopaminergic -a,-ARs constitute a multigene family. Three a,-AR subtypes have been cloned: the aiB from the hamster,'2 dog,13 rat,14-16 and human17'18; the aD from the rat'5'19 and human18; and the alc from the cow20 and human.18'2' In earlier studies, the mRNAs for two of these a,-AR subtypes were found in adult rat heart, the a1B1522 and the a1D.'5 Recently, we have shown that alc mRNA is also present in adult rat heart,23 contrary to prior reports.15,20,24 Thus, the mRNAs for all three cloned a,-ARs-the alB, the alD, and the ailc-are expressed in adult rat cardiac muscle.Two a,-AR subtypes had been defined by radioligand binding studies of native receptors in a variety of rat Received May 25, 1994; accepted July 29, 1994 tissues including the heart: the aClA and the a1B (for a review, see Reference 25). The cloned af, corresponds to the native alB-AR.'9'26'27 The cloned aiD, thought originally to correspond to the native alA,A' in fact appears to represent a distinct subtype.18"9'23'27 The cloned aic, thought originally to be an a,-AR not recognized in studies of native receptors,20.24 now appears to be the molecular equivalent of the native classical 1A. 18.23,27,28 Different physiological effects of a,-AR activation in the heart might be due not only to the presence of different a,-AR subtypes but also to a distinct distribution of a,-AR subtypes between cardiac myocytes and fibroblasts. Precedent exists for the presence of catecholamine receptors on cardiac fibroblasts. For example, 132-ARs are predominant on rat cardiac fibroblasts, wher...

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Section: Northern Blot Analysismentioning

confidence: 99%

Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

Stewart

Rokosh

Bailey

et al. 1994

Circulation Research

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“…al-Adrenoceptors belong to the superfamily of G protein-coupled receptors with seven transmembrane domains, and comprise a heterogeneous family. Molecular biological studies have identified three subtypes of ol-adrenoceptors (@ia, M1b, O1d) (Lomasney et al, 1991;Ramarao et al, 1992); Hirasawa et al, 1993). Among subtypes, human prostate has been shown to express predominantly CXla-adrenoceptors, and these mediate the contractile response, indicating that the ala-adrenoceptor may play an important role in the pathogenesis and treatment of BPH (Lepor et al, 1993;Price et al, 1993;Forray et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

α_1a‐Adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy

Shibata¹,

Hirasawa²,

Moriyama

et al. 1996

British J Pharmacology

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1 Two restriction fragment length polymorphisms of the human ala-adrenoceptor gene digested with PstI restriction enzyme exist; the nucleotide change causes the substitution of C residue for T at nucleotide 1441, thereby Arg492 to Cys492 transition, which might confer an additional putative palmitoylation site in the carboxy-terminal segment of the Xla-adrenoceptor. In the present study, we compared their pharmacological properties and examined whether this aa-adrenoceptor polymorphism is associated with benign prostatic hypertrophy (BPH).2 The frequency of ala-adrenoceptor polymorphism was not differently distributed between patients with benign prostatic hypertrophy (BPH) and normal subjects in Japan; thus, the relative frequencies of the C and T alleles were 0.90: 0.10 in normal male subjects (n=45) and 0.87: 0.13 in BPH patients (n=222), respectively. However, the frequency distribution of this polymorphism was significantly different between the Japanese and U.S. populations; thus, C and T alleles were 0.34 and 0.66 in U.S. populations.

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“…All three subtypes have been cloned from both rat and human cDNA libraries (Lomasney et al, 1991;Bruno et al, 1991;Ramarao et al, 1992;Laz et al, 1993;Hirasawa et al, 1993) and are expressed tissue-dependently in both species (Rokosh et al, 1994;Price et al, 1994 (Perez et al, 1991). Schwinn & Lomasney (1992) Perez et al (1991), and also had a different pharmacology from the a1A subtype.…”

Section: Introductionmentioning

confidence: 99%

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype

Marshall

Burt

Chapple

1995

British J Pharmacology

152

111

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1 The subtype of a1-adrenoceptor mediating contractions of human prostate to noradrenaline was characterized by use of a range of competitive and non-competitive antagonists. 2 Contractions of the prostate to either noradrenaline (pD2 5.5), phenylephrine (pD2 5.1) or methoxamine (pD2 4.4) were unaltered by the presence of neuronal and extraneuronal uptake blockers. Noradrenaline was about 3 and 10 times more potent than phenylephrine and methoxamine respectively. Phenylephrine and methoxamine were partial agonists. 3 Pretreatment with the alkylating agent, chlorethylclonidine (10-4 M) shifted the noradrenaline concentration-contraction curve about 3 fold to the right and depressed the maximum response by 31%. This shift is 100 fold less than that previously shown to be produced by chlorethylclonidine under the same conditions on OlB-adrenoceptor-mediated contractions. 4 Cumulative concentration-contraction curves for noradrenaline were competitively antagonized by WB 4101 (pA2 9.0), 5-methyl-urapidil (pA2 8.6), phentolamine (pA2 7.6), benoxathian (pA2 8.

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Cloning, Functional Expression and Tissue Distribution of Human cDNA for the α1C-Adrenergic Receptor

Cited by 154 publications

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Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

α_1a‐Adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype

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Cloning, Functional Expression and Tissue Distribution of Human cDNA for the α1C-Adrenergic Receptor

Cited by 154 publications

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Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

Cloning of the rat alpha 1C-adrenergic receptor from cardiac myocytes. alpha 1C, alpha 1B, and alpha 1D mRNAs are present in cardiac myocytes but not in cardiac fibroblasts.

α1a‐Adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy

Noradrenaline contractions of human prostate mediated by α1c‐(α1c‐) adrenoceptor subtype

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Product

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α_1a‐Adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy

Noradrenaline contractions of human prostate mediated by α_1c‐(α_1c‐) adrenoceptor subtype