A functional basis for classification of α-adrenergic receptors

Berthelsen, Spencer; Pettinger, William A.

doi:10.1016/0024-3205(77)90066-2

Cited by 811 publications

(213 citation statements)

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“…They are involved in the regulation of blood pressure by mediating contraction of vascular smooth muscle and induction of coronary vasoconstriction in humans (Civantos Calzada and Aleixandre de Artinano 2001; Comings et al 2000). These receptors also modulate sedation, analgesia, insulin release, renal function, cognition, memory, and behavior (Berthelsen and Pettinger 1977;McGrath et al 1989;Timmermans and van Zwieten 1981). Three distinct subtypes of a 2 -AR-a2A, a2B, and a2C-have been identified in multiple mammalian species by molecular and pharmacological research.…”

Section: Introductionmentioning

confidence: 99%

Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene

et al. 2004

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The alpha 2-adrenergic receptors (a 2 -AR) mediate physiological effects of epinephrine and norepinephrine. Three genes encode a 2 -AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325). We genotyped these functional markers plus a panel of single nucleotide polymorphisms evenly spaced over the gene regions to identify gene haplotype block structure. A total of 24 markers were genotyped in 96 Caucasians and 96 African Americans. ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size, respectively, in both populations. ADRA2C had one haplotype block of 10 kb in Caucasians only. For the three genes, haplotype diversity and the number of common haplotypes were highest in African Americans, but a similar number of markers (3-6) per block was sufficient to capture maximum diversity in either population. For each of the three genes, the haplotype was capable of capturing the information content of the known functional locus even when that locus was not genotyped. The a 2 -AR haplotype maps and marker panels are useful tools for genetic linkage studies to detect effects of known and unknown a 2 -AR functional loci.

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Section: Introductionmentioning

confidence: 99%

Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene

et al. 2004

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“…The a^ receptor is typically a postsynaptic niques it has often been suggested that some receptor which mediates smooth muscle contissues contain a mixture of Pi and pg recep-traction (12). The second messenger mediating tors.…”

Section: Molecular Events Following P Receptor Stimulationmentioning

confidence: 99%

“…ag Receptor stimulation inhibits norepinephrine release from the presynaptic termi-nal in the adrenergic nerve system (and thus exerts a sort of negative feedback regulation) and also inhibits acetylcholine release from the cholinergic nerve system (12,25). Furthermore, a^ receptors also mediate platelet aggregation, sedation, inhibition of renin release and inhibition of lipolysis in some species (12,27).…”

Section: Molecular Events Following P Receptor Stimulationmentioning

confidence: 99%

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Adrenoceptors: Molecular Nature and Role in Atopic Diseases

Djurup

1981

Allergy

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Since Szentivanyi proposed the idea that asthma and other atopic ditseases are due to a P adrenergic defect there has been much interest in the role of the adrenergic receptors in allergy. The radioactive ligand binding techniques developed within the last few years have greatly increased our knowledge concerning the molecular nature of the adrenoceptors and the events following receptor sdmulation. The adrenoceptors have shown to be very dynamic structures. Their number and affinity may be altered due to various physiological and pharmacological stimuli. Their role in the pathogenesis of atopic diseases has not been definitely settled, but there seem to be a true beta adrenergic hyporesponsiveness and alpha hyperresponsiveness in asthma. This article briefly describes the radioligand binding technique and summarizes our present knowledge of the nature of the alpha and beta adrenoceptors and their possible role in atopic diseases.Key words: adrenergic receptors; atopy; asthma. Accepted fcyr publication 11 January 1981, , , rr 1 , ^^ 01 receptor is defmed as a receptor for Functional subclassification of the adrenoceptorswhich epmephrme is a more potent stimulator It has been known since the beginning of the (agonist) than norepinephrine which again is century that the sympathomimetic amines have more potent than isoproterenol. The potency both excitatory and inhibitory effects in the of the amines was examined in intact animals organism. Early investigators proposed the or isolated organ preparations. In contrast, the existence of two fundamental types of mediator P receptor is defined as a receptor for which substances: an excitatory sympathin E and an isoproterenol is a more potent agonist than inhibitory sympathin I (1). As no amine which epinephrine which again is more potent than fulfilled the requirements for either sympathin norepinephrine. The development of relatively E or I could be found, the idea of two different selective a and |3 antagonists has further conreceptor types emerged. On the basis of the firmed the pharmacological usefulness of the a relative potency of six adrenergic amines on and P receptor concept. Table 1 summarizes various biological (mainly haemodynamic) pa-the major pharmacological characteristics of rameters, Ahlquist (1) defined two different the a and the j3 receptor. receptors: an a receptor which mediates most In 1967, Lands (55) showed that there is of the adrenergic amines' excitatory functions marked similarity between the relative poten-(vasoconstriction, pupil dilation, uterine con-cies of sympathomimetic amines on lipolysis traction) and a few inhibitory (intestinal relax-and cardiac stimulation on the one hand and ation), and a P receptor which mediates most of on bronchodilation and vasodepression on the the inhibitory functions (vasodilation, broncho-other. Furthermore, a potent lipolytic and cardilation, uterine relaxation) and a few excita-diac stimulating amine is a poor bronchodilator tory (cardiac inotropy and chronotropy).and vasodepressor. Therefore, Lands s...

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“…For this purpose, a classical pharmacological approach has been used, namely the detection of differences between the relative potencies of cx-adrenoceptor agonists and antagonists (Drew, 1977;Starke, 1977) in inducing prejunctional and postjunctional effects. On the basis of these pharmacological differentiation studies, adrenoceptors have been classified into two subtypes termed aland CX2-adrenoceptors (Berthelson & Pettinger, 1977). While prejunctional adrenoceptors belong to the cx2-subtype, recent evidence suggests that postjunctional receptors are not a homogeneous population and include both the oal-and C2-subtypes (Wikberg, 1979;DeMey & Vanhoutte, 1981; for review see McGrath, 1982).…”

Section: Introductionmentioning

confidence: 99%

Differences between the prejunctional effects of phenylephrine and clonidine in guinea‐pig isolated atria

Ledda

Mantelli

1984

British J Pharmacology

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1The prejunctional effects of clonidine and phenylephrine were studied in guinea-pig isolated atria by means of field stimulation of the sympathetic nerve terminals during the cardiac refractory period, in the presence of 1 pM atropine. 2 Clonidine (10-100nM) produced a dose-dependent decrease in the stimulus-inotropic response curve; the IC50 for clonidine was increased about 70 times by the pretreatment of the preparations with 1 tiM yohimbine. The effect of clonidine was not modified by 0.5 JiM prazosin. 3 Unlike clonidine, phenylephrine (1-10 fM) induced a statistically insignificant increase in the contractile force of preparations stimulated at 4 Hz. 4 The inhibitory effect of phenylephrine (1-10I1M) was partially prevented by either 1AM yohimbine or 0.5 jiM prazosin. However, it was antagonized, to about the same degree as that observed with clonidine, by the pretreatment of the preparations with both 1 JiM yohimbine and 0.5 AM prazosin. 5 The results seem to indicate that one component of the prejunctional effects of phenylephrine may be mediated by presynaptic oa-adrenoceptors belonging to the oci-subtype.

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A functional basis for classification of α-adrenergic receptors

Cited by 811 publications

References 46 publications

Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene

Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene

Adrenoceptors: Molecular Nature and Role in Atopic Diseases

Differences between the prejunctional effects of phenylephrine and clonidine in guinea‐pig isolated atria

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