Cloning of the cDNA for the human beta 1-adrenergic receptor.

Frielle, Thomas; Collins, Sheila; Daniel, Kiefer W.; Caron, Marc G.; Lefkowitz, Robert J.; Kobilka, Brian K.

doi:10.1073/pnas.84.22.7920

Cited by 527 publications

(240 citation statements)

References 31 publications

(29 reference statements)

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“…Additional evidence for β 1 involvement was the observation that norepinephrine was 6-fold more potent on a molar basis than epinephrine in stimulating ghrelin secretion (Fig. S4), a finding consistent with the differential affinities of the β 1 receptor for these agents (27).…”

Section: Discussionsupporting

confidence: 52%

Ghrelin secretion stimulated by β ₁ -adrenergic receptors in cultured ghrelinoma cells and in fasted mice

Zhao¹,

Sakata²,

Li³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

180

219

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Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding β 1 -adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective β 1 -adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on β 1 receptors on the ghrelinsecreting cells of the stomach.

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Section: Discussionsupporting

confidence: 52%

Ghrelin secretion stimulated by β ₁ -adrenergic receptors in cultured ghrelinoma cells and in fasted mice

Zhao¹,

Sakata²,

Li³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

180

219

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“…DNA Probes There were: (i) pADRAR, a 5.5 kb BamHI fragment of a genomic clone that included the 1.35 kb coding region of ADRA2R (16), which like all adrenoceptor genes lacks introns, and (ii) a 2.4 kb fulllength p1-AR cDNA clone inserted into the EcoRI site of pSP65 (17).…”

Section: Methodsmentioning

confidence: 99%

Association Analyses of RFLPs for the .ALPHA.2- and .BETA.1-Adrenoceptor Genes in Essential Hypertension.

1992

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Adrenoceptor stimulation has an important role in normal cardiovascular regulation and a genetic defect could be a cause of essential hypertension (HT). The present study examined the relationship with HT of RFLPs for the a2-adrenoceptor gene (ADRA2R) and N 1-adrenoceptor gene (ADRBIR), which share the same chromosomal locus (10g24-26). Subjects were HTs and normotensives (NTs) whose parents had a similar blood pressure status at age ? 50. The frequency of the minor allele of the DraI RFLP of ADRA2R was 0.17 in HTs (n =76) and 0.17 in NTs (n = 87). For the BglI RFLP of ADRBIR, frequency of the minor allele was 0.10 in HTs (n = 62) and 0.12 in NTs (n = 88). x 2 analysis showed no difference between HT and NT groups. Thus the present study provides no basis for involvement of the a2-or N 1-adrenoceptor genes in essential hypertension. (Hypertens Res 1992; 15: 57-60) Key Words:molecular genetics, sympathetic nervous system, alleles, blood pressureThe sympathetic nervous system has been implicated in the onset of essential hypertension (HT), as well as in the adaptation of the heart to chronically elevated blood pressure (BP) (1). At least part of the increase in BP in HT could be a result of an alteration in adrenoceptor number, affinity or signal transduction, either as a response to variation in local catecholamine concentrations or other factors, or could be due to a primary genetic disturbance. The possibility that decreased central a2-adrenoceptor (a2AR) density or responsiveness may be involved in HT is suggested by the efficacy of a2AR agonists as anti-HT agents (1). /9-adrenoceptor (/9AR) responsiveness is reduced in HT (2, 3) and could contribute to the increased peripheral vascular resistance (4-7). Decreased sensitivity could be caused by a primary genetic defect or be a result of tonic down-regulation of /9ARs in response to elevated sympathetic activity (3, 8) or be due to disruption in signal transduction (9) as a consequence of reduced function of the stimulatory guanosine triphosphate-binding protein (10) or PAR kinase (I1). j91ARs mediate the positive inotropic effect of /9AR agonists (12), and sympathetic stimulation of renin secretion (13), so that defects could result in failure of the heart to adapt to an increased pressure load, increased peripheral resistance (6-9), and the low plasma renin seen in a large proportion of HT patients (14).Although the role of adrenoceptors in HT has been a subject of intense investigation by many groups, no study to date has addressed the important question of primary involvement of a variant of one of the adrenoceptor genes, nor of any other neural gene, in disease onset. In the present work we examined the a2-AR gene (ADRA2R) and the P1AR gene (ADRA1R), which share the same locus on chromosome 10 (q24-q26) (cf. the a l-and /92-adrenoceptor genes, which are located at chromosome 5831-q32) (15). MethodsStudy Design All subjects were adult Caucasian. HT patients were selected on the basis of correct diagnosis of essential HT in accord with conventional crite...

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“…14 However, the cytoplasmic regions of the receptors, which interact with other cellular proteins to mediate various signaling events, are considerably more divergent. 14 In fact, Liggett et al have previously called attention to polyproline stretches present in the third cytoplasmic loop of ␤ 1 ARs but not ␤ 2 ARs. 15 Swapping of this region between the ␤ 1 ARs and ␤ 2 ARs significantly altered their signaling properties.…”

Section: See P 1707mentioning

confidence: 99%

Catecholamines, Cardiac β-Adrenergic Receptors, and Heart Failure

2000

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Cloning of the cDNA for the human beta 1-adrenergic receptor.

Cited by 527 publications

References 31 publications

Ghrelin secretion stimulated by β ₁ -adrenergic receptors in cultured ghrelinoma cells and in fasted mice

Ghrelin secretion stimulated by β ₁ -adrenergic receptors in cultured ghrelinoma cells and in fasted mice

Association Analyses of RFLPs for the .ALPHA.2- and .BETA.1-Adrenoceptor Genes in Essential Hypertension.

Catecholamines, Cardiac β-Adrenergic Receptors, and Heart Failure

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Cloning of the cDNA for the human beta 1-adrenergic receptor.

Cited by 527 publications

References 31 publications

Ghrelin secretion stimulated by β 1 -adrenergic receptors in cultured ghrelinoma cells and in fasted mice

Ghrelin secretion stimulated by β 1 -adrenergic receptors in cultured ghrelinoma cells and in fasted mice

Association Analyses of RFLPs for the .ALPHA.2- and .BETA.1-Adrenoceptor Genes in Essential Hypertension.

Catecholamines, Cardiac β-Adrenergic Receptors, and Heart Failure

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Ghrelin secretion stimulated by β ₁ -adrenergic receptors in cultured ghrelinoma cells and in fasted mice

Ghrelin secretion stimulated by β ₁ -adrenergic receptors in cultured ghrelinoma cells and in fasted mice