Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 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.
 ...
PMID:The rat angiotensin II AT1A receptor couples with three different signal transduction pathways. 137 99

Arterial constriction by angiotensin II (Ang II) in the human forearm is inhibited by the infusion of the AT1-receptor antagonist losartan. We investigated venous constriction by Ang II in the forearm of 19 healthy subjects (23 +/- 1 years) and the inhibitory effects of losartan. Furthermore, we investigated, in both the arterial and venous systems, whether the constrictor effects of Ang II are calcium influx dependent by determining the influence of nicardipine. Arterial forearm blood flow (FBF) and maximal venous outflow (MVO) were measured by venous-occlusion plethysmography. Sodium nitroprusside (5-12.5 ng/kg/min) was infused to predilate the forearm vasculature. Ang II (0.1, 1, and 10 ng/kg/min) was infused before and during losartan (0.3 and 3 microg/kg/min) or nicardipine (0.05 and 0.15 microg/kg/min), respectively. Ang II decreased FBF (Emax-FBF) by 79 +/- 4% and MVO (Emax-MVO) by 28 +/- 3% (p < 0.05). Nicardipine at 0.05 and 0.15 microg/kg/min reduced Emax-FBF from -79 +/- 4% to -48 +/- 4% and -6 +/- 2%, respectively (p < 0.05). Losartan in both doses completely inhibited Emax-MVO (p < 0.05), whereas nicardipine did not influence the venoconstriction by Ang II (p > 0.05). In conclusion, Ang II causes a constriction of both arteries and veins in the human forearm, which may be inhibited by losartan. The arterial constriction appears to be caused by an AT1-receptor-mediated calcium influx via L-type calcium channels. In contrast, the venoconstrictor effect of Ang II proved insensitive to the calcium antagonist nicardipine.
 ...
PMID:Venoconstriction by angiotensin II in the human forearm is inhibited by losartan but not by nicardipine. 945 77

In the human forearm vascular bed, the arterial constrictor effects of angiotensin II were found to be caused by an AT1-receptor mediated calcium influx, while the venous constrictor effects appeared to be independent of L-type calcium channels. In this study, we investigated the influences of the AT1-receptor antagonist losartan and the calcium channel blocker nicardipine on the angiotensin II-induced constriction of small isolated subcutaneous arteries and veins obtained from human mammary tissue. Subcutaneous arteries and veins were isolated from mammary tissue from 9 healthy women who underwent breast reduction surgery. Effects of angiotensin II (0.3 nM to 1 mM), losartan (0.1 mM) and nicardipine (0.1 mM) were investigated in a myograph set up. Identification of arteries and veins was confirmed histologically after the experiments. Drug effects were expressed relatively to the potassium-induced contraction. Angiotensin II concentration-dependently contracted arteries and veins by maximally 1.66 +/- 0.31 N/m and 0.43 +/- 0.08 N/m, respectively (P < 0.05). In arteries the angiotensin II were subject to a mild degree of tachyphylaxis: the Emax of the repetitive concentration-response curve (CRC) was reduced from 105 +/- 4% of the potassium-induced contraction to 84 +/- 6% (P < 0.05); the EC50 value was unchanged (P > 0.05). In veins no tachyphylaxis was observed. Losartan caused a rightward shift of the CRC of angiotensin II in arteries and veins (P < 0.05), and reduced the Emax in arteries from 105 +/- 4 to 85 +/- 9% (P < 0.05), but did not change the Emax in veins. Nicardipine significantly decreased the Emax in arteries and veins (to residual values of 10 +/- 2 and 20 +/- 4%, respectively, of the control values). In conclusion, the angiotensin II-induced constriction of human arteries and veins isolated from mammary tissue are AT1-receptor mediated and inhibited by losartan. The nearly complete inhibition by nicardipine indicates that the constrictor effects in both types of vessels are dependent on L-type calcium channels.
 ...
PMID:Influence of losartan and nicardipine on the contractile responses of human subcutaneous arteries and veins to angiotensin II. 1002 87