Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine whether the subpopulation of the rat type 1 angiotensin II (AII) receptor (AT1A) couples with a single or multiple signal transduction pathways, we constructed Chinese hamster ovary (CHO) cell lines producing the recombinant receptor. The expressed AT1A receptor exhibits typical pharmacological characteristics of the AT1 receptor, known to mediate the main physiological function of AII. Addition of AII to the CHO cells induced a rapid, transient increase in intracellular free Ca2+ concentrations ([Ca2+]i) followed by a lower, sustained phase. Nicardipine, a blocker of voltage-dependent L-type Ca2+ channels, attenuated the transient [Ca2+]i response and abolished the sustained phase. The transient phase was also reduced dose-dependently by the phospholipase C inhibitor neomycin. Furthermore, AII inhibited forskolin-evoked cAMP accumulation. These data suggest, although another subpopulation named AT1B is present, that the rat AT1A receptor can independently couple with all three signal transduction pathways known to be induced by AII: i.e., i) activation of phospholipase C resulting in InsP3 generation with a subsequent release of intracellularly stored Ca2+, ii) activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels, and iii) inhibition of adenylate cyclase activity.
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PMID:The rat angiotensin II AT1A receptor couples with three different signal transduction pathways. 137 99

ISOFORMS OF ANGIOTENSIN II RECEPTORS: So far, three isoforms of angiotensin II receptors have been identified by complementary DNA cloning, all with seven transmembrane domain structures. AT1A and AT1B are the most common isoforms. They are coupled to phospholipase C through Gq/G11 proteins and to a calcium channel, and negatively coupled to adenyl cyclase. AT2 is only remotely related to the AT1 family. KNOWN STRUCTURAL DETAILS OF ANGIOTENSIN II RECEPTORS: Ligand-binding domains are being defined in the space surrounded by transmembrane helices. Coupling to Gq seems to involve the second cytosolic loop. Receptor proteins undergo transition to a low-affinity form, which is desensitized and internalized. CHROMOSOME LOCATION: In the rat, AT1A, AT1B and AT2 are located on chromosomes 17, 2 and X, respectively. SIGNALING PATHWAY: Studies with receptors are revealing several different pathways of angiotensin signaling that modulate protein tyrosine phopsphorylation.
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PMID:Molecular biology of angiotensin II receptors: an overview. 776 96