Disease relevance of Adra1d

• As with the previous in vitro and in situ models, hypertension (30 days) had no effect on expression of alpha 1B- and alpha 1D-adrenergic receptor mRNAs in the suprarenal aorta compared with sham coarctation [1].
• 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 [2].
• The alpha 1A-adrenergic receptor subtype mediates biochemical, molecular, and morphologic features of cultured myocardial cell hypertrophy [3].
• Vascular alpha 1D-adrenoceptor function is maintained during congestive heart failure after myocardial infarction in the rat [4].
• Recent advances in the use of young pre-hypertensive rats and adult spontaneously hypertensive rats with one kidney and Grollman-type renal hypertension suggest vascular alpha 1D-adrenoceptor involvement in the increased blood pressure [5].

High impact information on Adra1d

• Cross talk between angiotensin AT1 and alpha 1-adrenergic receptors: angiotensin II downregulates alpha 1a-adrenergic receptor subtype mRNA and density in neonatal rat cardiac myocytes [6].
• High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the alpha 1A receptor subtype [7].
• Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique alpha 1-adrenergic receptor pharmacology [7].
• The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors [7].
• Molecular cloning and expression of the cDNA for the alpha 1A-adrenergic receptor. The gene for which is located on human chromosome 5 [7].

Biological context of Adra1d

• In the present study, we quantified alpha-1a, alpha-1b and alpha-1d adrenergic receptor mRNA in 19 adult rat tissues through the use of reverse transcription (RT) and a competitive polymerase chain reaction (PCR) [8].
• The agreement observed between agonist potency at the rat aorta and affinity for the alpha 1d binding site provide new evidence that the alpha 1D-adrenoceptor subtype is responsible for mediating contractions in the rat aorta [9].
• These results suggest that PPA does not act via the alpha 1a-Adrenergic receptor subtype to suppress food intake [10].
• The alpha 1D-adrenoceptor subtype is predominantly involved in the contraction of a variety of vessels and its role in the control of blood pressure has been suggested, a phenomenon probably related to aging [5].

Anatomical context of Adra1d

• The results revealed that the relative abundance of alpha-1a adrenergic receptor mRNA among various tissues was as follows: vas deferens > colon > or = stomach > or = cerebral cortex > heart > or = small intestine > or = testis > prostate [8].
• The relative rank order of alpha-1b adrenergic receptor mRNA expression was heart > or = cerebral cortex > liver, whereas that of alpha-1d adrenergic receptor mRNA was vas deferens > cerebral cortex > or = aorta > adrenal gland.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• 1) mRNA for the novel alpha 1D-adrenoceptor is localized in vascular smooth muscle [11].
• However, the low affinity site had ligand binding characteristics distinct from those of the alpha 1D-adrenoceptor or any other known alpha 1-adrenoceptor subtype. mRNA for the alpha 1B- and alpha 1C-adrenoceptors was also detected in the aorta, renal arteries, and mesenteric resistance arteries [11].
• 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 [12].

Associations of Adra1d with chemical compounds

• The effects of tamsulosin, a high affinity antagonist at functional alpha 1A- and alpha 1D-adrenoceptor subtypes [13].
• High concentrations of the alpha 1D-adrenoceptor antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl) 1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride), displaced bound [3H]prazosin in a single-site manner and the binding affinity was close to those for alpha 1A- and alpha 1B-adrenoceptor binding sites [14].
• All the antagonists shifted to the right the concentration-response curve to methoxamine. pA2 values indicate that all arteries but caudal express the alpha 1D-adrenoceptor subtype, since BMY 7378 values were high in these arteries [15].
• WB4101 (N-[2-(2, 6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin-2-m ethanamine) is a competitive antagonist that is selective for alpha 1A- and alpha 1C-adrenoceptors, while chloroethylclonidine is an irreversible blocker that is reported to antagonize alpha 1B-, alpha 1C-, and alpha 1D-adrenoceptor binding [16].
• The rank order of potency at the rat aorta was the same as that obtained for binding affinity at the rat clonal alpha 1d-adrenoceptor: norepinephrine > epinephrine > cirazoline > phenylephrine > oxymetazoline > A-61603 > methoxamine [9].

Physical interactions of Adra1d

• 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 [9].

Regulatory relationships of Adra1d

• Alpha-1A adrenergic receptor stimulation with phenylephrine promotes arachidonic acid release by activation of phospholipase D in rat-1 fibroblasts: inhibition by protein kinase A [17].

Other interactions of Adra1d

• 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 [18].
• Amplifying effect of the selective calmodulin antagonist, calmidazolium, on the potency of nifedipine to inhibit alpha 1D-adrenoceptor-mediated contraction in the rat aorta [19].

Analytical, diagnostic and therapeutic context of Adra1d

• In situ hybridization with an antisense probe localized the mRNA for the alpha 1D-adrenoceptor to the medial layer of the rat aorta renal and mesenteric resistance arteries [11].
• These results from cell culture, organ culture, and in vivo models suggest that pressure (load) alone has no effect on alpha 1B- and alpha 1D-adrenergic receptor expression [1].
• 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 [20].
• Sympathectomy reveals alpha 1A- and alpha 1D-adrenoceptor components to contractions to noradrenaline in rat vas deferens [21].

References