Molecular Cloning and Expression of a New Alpha-1-Adrenergic Receptor Subtype

Schwinn, Debra A.; Cotecchia, Susanna; Lomasney, Jon W.; Caron, Marcg .; Lefkowitz, Robert J.

doi:10.1213/00000539-199002001-00359

Cited by 101 publications

(143 citation statements)

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“…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: 95%

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: 95%

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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“…The alc clone is now considered to represent the classical a1A subtype found in tissues (Laz et al, 1993;Perez et al, 1994;Burt et al, 1995). The al clone was originally isolated from a bovine brain cDNA library and although it had a very similar pharmacology to the OClA-adrenoceptor, it was thought to represent a new subtype as it was also chlorethylclonidine-sensitive (Schwinn et al, 1990). However, the degree to which it is sensitive to chlorethylclonidine has been questioned recently and it may only be partially sensitive, at least in the rat (Forray et al, 1994a (Arunlakshana & Schild, 1959).…”

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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“…The a1b adrenoceptor subtype has been cloned from cultured smooth muscle cells in hamsters, 16 from rat brain 17 and from humans. 18 The a1c adrenoceptor subtype has been identi®ed in bovine brain 19 and from humans tissues. 20 The a1d adrenoceptor subtype has been cloned from rat and human brains.…”

Section: Introductionmentioning

confidence: 99%

Expression of α1 adrenoceptor subtypes in rat corpus cavernosum

Véronneau-Longueville

Rampin

Jardin

et al. 1998

Int J Impot Res

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Norepinephrine mediates the antierectile role of the sympathetic nervous system. It binds to postsynaptic a1 adrenoceptors present on smooth muscle ®bers of the corpus cavernosum. Receptor cloning studies have evidenced three a a1 adrenoceptor subtypes: a a1A, a a1B and a1D. We searched for the presence of these three a a1 adrenoceptor subtypes in the rat corpus cavernosum using in situ hybridization with speci®c oligonucleotide probes. Brain tissue was used as the reference of probes speci®city. Autoradiographic ®lms were studied with light illumination and computer-assisted densitometry using an image analyser. We provide evidence that the three a a1 adrenoceptor subtypes are expressed in the rat corpus cavernosum. These three subtypes appear to be more expressed in the trabecular smooth muscle ®bers than in vascular smooth muscle ®bers. Further experiments are needed to determine whether the proportion of a a1 adrenoceptor subtypes changes according to the etiology of erectile dysfunction. This morphological approach provides a basis for future pharmacological research of speci®c a a1 adrenoceptor subtypes blocking agents designed to treat erectile dysfunction.

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Molecular Cloning and Expression of a New Alpha-1-Adrenergic Receptor Subtype

Cited by 101 publications

References 0 publications

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.

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

Expression of α1 adrenoceptor subtypes in rat corpus cavernosum

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Molecular Cloning and Expression of a New Alpha-1-Adrenergic Receptor Subtype

Cited by 101 publications

References 0 publications

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.

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

Expression of α1 adrenoceptor subtypes in rat corpus cavernosum

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