Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bradykinin (BK) and its analogues induce a typical biphasic response (relaxation followed by contraction) in the isolated rat duodenum. We studied the role of B1 and B2 BK receptors and nitric oxide (NO) in relaxation and contraction of the isolated rat duodenum. Both effects are concentration-dependent: BK has shown an EC50 (contraction) of 3.8 +/- 1.9 x 10(-7) M and an IC50 (relaxation) of 3.0 +/- 0.7 x 10(-9). Similar results were obtained with the selective B2 receptor agonists [Hyp3,Tyr(Me)8]-BK and [Phe8 psi (CH2-NH)Arg9]-BK, showing an EC50 of 9.6 +/- 1.9 x 10(-7) M and 5.6 +/- 2.9 x 10(-7) M and an IC50 of 3.5 +/- 0.6 x 10(-10) M and 6.8 +/- 1.7 x 10(-10) M, respectively. Furthermore, the effects induced by these three agonists were not altered when tissues were treated with 42.1 microM Mergetpa, a carboxypeptidase N inhibitor. While the relaxant and contractile effects elicited by BK were significantly inhibited in the presence of Hoe 140 (0.7 microM), a selective B2 receptor antagonist, those induced by the selective B1 receptor agonist desArg9-BK were not. Furthermore, [Leu8]-desArg9-BK (2.6 microM), which is both a pure and selective B1 receptor antagonist, acted as an agonist on the rat duodenum, inducing a biphasic relaxant and contractile effect. These relaxant and contractile effects were not altered by drugs that inhibit or stimulate NO production, such as L-NAME (200 microM), a combination of L-NAME (200 microM) and indomethacin (2.5 microM), L-arginine (1 mM), or superoxide dismutase (20 U/ml). However, the contractile effect was significantly reduced when tissues were preincubated with methylene blue (100 microM), which inhibits activation of guanylate cyclase. We conclude that 1) BK and its analogues selectively activate a B2 receptor, producing a biphasic effect (relaxation and contraction); 2) DesArg9-BK may either acts via a different receptor which might be another B1 receptor subtype or a typical B1 receptor where [Leu8]-desArg9-BK acts as a partial agonist; and 3) neither NO nor the prostaglandin pathway mediates BK-induced relaxation in the isolated rat duodenum.
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PMID:Role of B1 and B2 receptors and of nitric oxide in bradykinin-induced relaxation and contraction of isolated rat duodenum. 752 22

Chronic, low-level lead exposure causes hypertension in both animals and humans. The pathogenesis of lead-induced hypertension is multifactorial, including such diverse mechanisms as: inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species (ROS), leading to a functional deficiency in nitric oxide; heightened sympathetic activity and plasma norepinephrine together with depressed vascular and elevated renal beta-adrenergic receptor density; elevated plasma angiotensin-converting enzyme (ACE) activity, plasma renin activity (PRA), angiotensin II (Ang-II), and aldosterone levels; increased kininase I and kininase II activities; lead-induced inhibition of vascular smooth muscle Na(+)-K+ ATPase, leading to a rise in cellular Na+ and, hence, Ca2+; and a possible rise in endothelin and thromboxane generation. In this article, we present an overview of the epidemiology and proposed underlying mechanisms of lead-induced hypertension.
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PMID:Lead-induced hypertension: role of oxidative stress. 1525 67