Disease relevance of Adra1a

• Cloning and characterization of the rat alpha 1a-adrenergic receptor gene promoter. Demonstration of cell specificity and regulation by hypoxia [1].
• CONCLUSIONS: (1) the exacerbation of reperfusion induced arrhythmias by alpha 1 adrenergic stimulation during ischaemia is mediated by the alpha 1A adrenoceptor subtype, and (2) increased Na+/H+ exchanger activity during ischaemia and reperfusion may play a causal role in this phenomenon [2].
• Inhibition by pretreatment with pertussis toxin is in agreement with involvement of the alpha 1A-adrenoceptor subtype in this Ca(2+)-dependent effect [3].
• Synthesis and pharmacological characterization of 3-[2-((3aR,9bR)-cis-6-methoxy-2,3,3a,4,5,9b-hexahydro-1H-benz[e] isoindol-2-yl)ethyl]pyrido-[3',4':4,5]thieno[3,2-d]pyrimidine-2,4 (1H,3H)-dione (A-131701): a uroselective alpha 1A adrenoceptor antagonist for the symptomatic treatment of benign prostatic hyperplasia [4].

Psychiatry related information on Adra1a

• Repeated imipramine and electroconvulsive shock increase alpha 1A-adrenoceptor mRNA level in rat prefrontal cortex [5].

High impact information on Adra1a

• 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 [6].
• 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 [7].
• The alpha 1a adrenergic receptor subtype antagonist WB 4101 abolished noradrenaline stimulated inositol phosphate generation in myocytes, whereas chlorethylclonidine at large doses only partially inhibited this response [8].
• Electroconvulsive shock increases alpha 1b- but not alpha 1a-adrenoceptor binding sites in rat cerebral cortex [9].
• Systemic alpha 1A-adrenoceptor antagonist inhibits neointimal growth after balloon injury of rat carotid artery [10].

Chemical compound and disease context of Adra1a

• The effect of phenylephrine on the L-type current was not abolished in cells pretreated with pertussis toxin and cholera toxin, indicating that pertussis toxin- and cholera toxin-insensitive G-proteins are coupled to the alpha-1A adrenoceptor [11].

Biological context of Adra1a

• This pattern of agonist and blocking drug interaction suggests that the renal postjunctional alpha 1-adrenoceptors require extracellular calcium and are sensitive to 5-methylurapidil, characteristics of the alpha 1a-adrenoceptor subtype [12].
• The alpha 1-adrenoceptor population in the heart was characterized by competitive binding experiments using [3H]prazosin and the alpha 1A-adrenoceptor-selective antagonist 5-methyl urapidil [13].
• The effects of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane sulfonanilide hydrochloride), an alpha 1A-adrenoceptor-selective agonist, on intraurethral pressure and blood pressure were investigated in anesthetized dogs [14].
• Doxazosin-induced up-regulation of alpha 1A-adrenoceptor mRNA in the rat lower urinary tract [15].
• Tissue distribution of NS-49, a phenethylamine class alpha 1A-adrenoceptor agonist, in pigmented rats [16].

Anatomical context of Adra1a

• 1. We have studied the alpha 1-adrenoceptor subtypes mediating inotropic effects of adrenaline in rat right ventricle and the Ca2+ sources used to elicit these effects. alpha 1A-Adrenoceptor-mediated contractile effects in rat vas deferens were studied for comparison in some cases [17].
• 3. Half of the compounds displacing [3H]-prazosin bound to guinea-pig cerebral cortex membranes display alpha 1A-adrenoceptor selectivity [18].
• 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 [19].
• The high-affinity constant for WB4101 (1.4 nM) in 1-month-old aorta was consistent with that for alpha 1d adrenoceptor subtype, whereas the high-affinity constants (0.03 nM) in 6- and 24-month-old aortas were consistent with those for the alpha 1a adrenoceptor subtype [20].
• 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 [18].

Associations of Adra1a with chemical compounds

• 4. Schild analysis of inhibition experiments with the alpha 1A-adrenoceptor-selective antagonists, 5-methyl-urapidil and (+/-)-tamsulosin, demonstrated that adrenaline causes its inotropic effects mainly via the alpha 1B-adrenoceptor subtype [17].
• Another group was continuously infused with the irreversible selective alpha 1a-adrenoceptor antagonist, SZL-49 (10 micrograms kg-1 h-1) for 1 h, prior to the construction of dose-response curves to phenylephrine [21].
• WB4101, a marginally alpha-1A adrenoceptor selective antagonist, 5-methyl-urapidil, a highly alpha-1A adrenoceptor selective antagonist and chloroethylclonidine, a highly alpha-1B adrenoceptor selective antagonist, all inhibited both contractile phases [22].
• 5. Selective protection of a putative alpha 1A-adrenoceptor population against the irreversible action of phenoxybenzamine also failed to increase the potency of RS-17053 (pA2 = 8.25 +/- 0.06 against A61603) [23].
• However, it had no significant effects on norepinephrine (NE)-stimulated [3H]IP1 formation or alpha 1A-adrenoceptor subtype [24].

Physical interactions of Adra1a

• Correlation coefficients comparing the clonal alpha 1d-adrenoceptor binding affinity to in vitro contractile responses were 0.03 and 0.10 for the rat vas deferens and canine prostate alpha 1A-adrenoceptor responses, respectively, 0.09 for the rat spleen alpha 1B and as noted, 0.94 for the rat aorta [25].

Other interactions of Adra1a

• 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 [26].
• 5-HT1A receptors and the tail-flick response. VI. Intrinsic alpha 1A-adrenoceptor antagonist properties can mask the actions of 5-HT1A receptor agonists in the spontaneous tail-flick paradigm [27].
• Synergism between beta 2-adrenoceptor agonists and subtype-selective alpha 1A-adrenoceptor antagonists in the tocolytic effect on pregnant rat uterus in vitro [28].

Analytical, diagnostic and therapeutic context of Adra1a

• We have isolated from rat lung, by polymerase chain reaction techniques, a cDNA fragment corresponding to the third intracellular domain of the alpha 1c adrenergic receptor subtype [29].
• The effects of intrathecal injection of tamsulosin (an alpha-1A adrenergic receptor antagonist) and naftopidil (an alpha-1D adrenergic receptor antagonist) on isovolumetric bladder contraction were investigated in rats under urethane anesthesia [30].
• The present study confirms an increase in alpha 1-adrenoceptors in rat myocardium after chemical denervation and reveals that the effect is almost completely confined to the alpha 1A-adrenoceptor subtype [31].
• The metabolism of NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoro-methanesulfonanilide++ + hydrochloride, CAS 137431-04-0), a phenethylamine class alpha 1A-adrenoceptor agonist, was investigated in rats, rabbits, dogs, and monkeys after single intravenous or oral administration of 14C-NS-49 or unlabeled NS-49 [32].

References