Disease relevance of Adra1b

• WB4101, a selective antagonist of alpha 1A adrenergic receptor subtype, but not chlorethylclonidine, a selective antagonist of alpha 1B adrenergic receptor subtype, inhibited phenylephrine (an alpha 1 adrenergic agonist)-induced situs inversus [1].
• This study examined the contribution of phosphatidylinositol metabolism and the efficacy of protein kinase C-mediated desensitization in the exaggerated alpha 1b-adrenergic receptor-mediated inositol phosphate response in the aorta of the deoxycorticosterone acetate (DOCA)-salt rat model of hypertension [2].
• In rat myocardium hypothyroidism decreased alpha 1b-adrenoceptor binding sites [3].
• Hypoxia/reoxygenation selectively impairs alpha 1b-adrenoceptor function in small mesenteric arteries [4].

High impact information on Adra1b

• To elucidate the molecular mechanism of the stimulatory effect of thyrotropin on the gene regulation of alpha 1B adrenergic receptor in functioning rat thyroid (FRTL-5) cells, we established a competitive reverse-transcriptase (RT) polymerase chain reaction (PCR) and nuclear run-off assay to quantify changes in mRNA levels and transcription rates [5].
• The rat alpha 1B adrenergic receptor gene middle promoter contains multiple binding sites for sequence-specific proteins including a novel ubiquitous transcription factor [6].
• Truncation of the receptor carboxyl terminus impairs agonist-dependent phosphorylation and desensitization of the alpha 1B-adrenergic receptor [7].
• The alpha 1B-adrenergic receptor (alpha 1BAR) and its truncated mutant T368 lacking the last 147 amino acids were stably expressed in Rat1 fibroblasts [7].
• Wheel running alters serotonin (5-HT) transporter, 5-HT1A, 5-HT1B, and alpha 1b-adrenergic receptor mRNA in the rat raphe nuclei [8].

Biological context of Adra1b

• However, no changes were detected in expression of either alpha 1D- or alpha 1B-adrenergic receptor mRNAs or receptor density after 24 to 48 hours of loading. beta-Actin and SMC-specific alpha-actin mRNA, as well as cell number and per-cell total RNA and protein, were also unaffected [9].
• We previously reported that a novel GTP binding protein (G alpha h) is tissue type transglutaminase (TGII) and transmits the alpha 1B-adrenoceptor (AR) signal to phospholipase C (PLC) through its GTPase function [10].
• The low-affinity constants for WB4101 (31-51 nM) were consistent with those for the alpha 1b adrenoceptor subtype, and this binding site decreased with age [11].
• The alpha 1b-adrenoceptor alkylating agonist chloroethylclonidine (5 micrograms kg-1 plus 1.25 micrograms kg-1 h-1 and twice this dose) attenuated renal nerve-mediated vasoconstrictions by 20% (p < 0.01), but not those induced by PE and methoxamine [12].
• We conclude that the pharmacologically defined alpha 1A- and alpha 1B-adrenoceptor subtypes are both coupled to PI hydrolysis in the ventricular myocyte [13].

Anatomical context of Adra1b

• Alpha 1B-adrenoceptor-mediated excitation of piriform cortical interneurons [14].
• Separation of putative alpha 1A- and alpha 1B-adrenoceptor mediated components in the tension response of the rat vas deferens to electrical field stimulation [15].
• The affinities of selective compounds for the alpha 1B-adrenoceptor subtype in guinea-pig cerebral cortex correlate very well with their affinity for alpha 1B-adrenoceptor in the rat spleen homogenate [16].
• 5. Spiperone exhibited 12.9 fold higher affinity for rat liver alpha 1B-adrenoceptors than for rat submaxillary gland alpha 1A-adrenoceptor and may therefore represent the first alpha 1B-adrenoceptor selective ligand [17].
• The alpha 1-adrenoceptor population of rat thoracic aorta is predominantly of the alpha 1A-adrenoceptor subtype, and in guinea-pig thoracic aorta it is mainly of the alpha 1B-adrenoceptor subtype [16].

Associations of Adra1b with chemical compounds

• Two other groups of rats were continuously infused with the irreversible selective alpha 1b-adrenoceptor antagonist, chloroethylclonidine (3 mg kg-1 h-1) for 1 h, prior to the construction of dose-response curves to phenylephrine or methoxamine [18].
• 3. The putative alpha 1L-adrenoceptor antagonist JTH-601, but not the alpha 1B-adrenoceptor antagonist chloroethylclonidine (10 microM) antagonized noradrenaline-induced contractions of SMA [19].
• The effects of 5-methylurapidil (5-MU), an alpha-1a adrenoceptor antagonist, and chloroethyl-clonidine (CEC), an alpha-1b adrenoceptor antagonist, on contractile responses were determined [20].
• Displacement isotherms for amidephrine, benoxathian, oxymetazoline, phentolamine and WB 4101 were biphasic and were consistent with the presence of both alpha 1A- and alpha 1B-adrenoceptor subtypes as described by Morrow & Creese (1986) and Han et al [17].
• We conclude that most tamsulosin metabolites are high potency antagonists at the alpha-1 adrenoceptors and retain the alpha-1A over the alpha-1B adrenoceptor selectivity of tamsulosin [21].

Physical interactions of Adra1b

• It was 36-fold selective for the alpha 1A- versus alpha 1B-adrenoreceptor and 60- and 20-fold selective in binding to the alpha 1a-adrenoreceptor relative to alpha 1b and alpha 1d subtypes, respectively [22].
• Alpha 1B-adrenoceptor interacts with multiple sites of transglutaminase II: characteristics of the interaction in binding and activation [10].
• Both the cyclic AMP response element and the activator protein 2 binding site mediate basal and cyclic AMP-induced transcription from the dominant promoter of the rat alpha 1B-adrenergic receptor gene in DDT1MF-2 cells [23].

Regulatory relationships of Adra1b

• A marginal role of calcium in the alpha 1b-adrenoceptor phosphorylation induced by endothelin-1 cannot be discarded [24].

Other interactions of Adra1b

• Pharmacological techniques have defined the existence of two different alpha 1-adrenoceptors, the alpha 1A- and alpha 1B-adrenoceptor subtypes and both of these receptors have been cloned in addition to a cloned alpha 1d-adrenoceptor [14].
• No changes in alpha 1B-adrenoceptor or beta/gamma-actin steady-state mRNA levels were observed in H4IIE cells, a nonvascular, immortalized cell line [25].
• Both alpha 1b-adrenergic receptor mRNAs appear to share extensive regions of homology, therefore, we used oligonucleotide-directed ribonuclease H mapping to detect sequence differences between the two transcripts [26].

Analytical, diagnostic and therapeutic context of Adra1b

• The alpha 1B-adrenergic receptor mRNA was detected for the first time in rat Glm, PCT, PST and TAL using RT-PCR. alpha 1BAR mRNA seems to be expressed in the specific sites along the nephron and may play significant roles in renal functions, although the specific physiological effects of the renal alpha 1B-adrenergic receptor are unknown [27].
• In these microvessels, isolated by perfusion with iron, alpha 1B-adrenergic receptor mRNA levels (by ribonuclease protection assay) were similar in SHR and WKY rats [28].
• Increased alpha 1B-adrenoreceptor mRNA levels in the rat kidney after thyroidectomy [29].
• Functional change of the balance between alpha 1A and alpha 1B adrenoceptor populations after transplantation of the vas deferens to the intestine [30].
• By Northern blot analysis, Clone 9 cells expressed a 2.7 kb alpha 1b-adrenergic receptor gene transcript whereas two transcripts, 3.3 kb and 2.7 kb, were observed in total cellular RNA isolated from rat liver [31].

References