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)

Vasoconstrictor responses to sympathetic nerve stimulation and their sensitivity to metabolic modulation reportedly differ in fast-twitch and slow-twitch muscles, but the underlying mechanisms are not known. Both alpha(1)- and alpha(2)-adrenoceptors mediate these vascular responses in fast-twitch muscle, while their roles in slow-twitch muscle are less well defined. In this study, the phosphorylation of smooth muscle myosin regulatory light chain (smRLC) was measured as an index of vasoconstriction in slow-twitch soleus muscles and fast-twitch extensor digitorum longus (EDL) muscles isolated from C57BL/6J mice. In soleus muscles, incubation with phenylephrine (PE) or UK 14,304 to selectively activate alpha(1)- or alpha(2)-adrenoceptors resulted in concentration-dependent increases in smRLC phosphorylation. To evaluate metabolic modulation of these responses, vasodilator pathways previously implicated in such modulation in fast-twitch muscle were activated in soleus muscles by treatment with the nitric oxide (NO) donor nitroprusside or the ATP-sensitive potassium (K(ATP)) channel opener cromakalim. Both drugs inhibited responses to UK 14,304, but not to PE. The effect of nitroprusside to antagonize UK 14,304 responses was prevented by inhibition of guanylyl cyclase or by blockade of K(ATP) channels, but not by blockade of other potassium channels. Results were similar in EDL muscles. These data provide the first evidence for alpha(2)-adrenoceptor-mediated constriction in slow-twitch muscle, and show that it is sensitive to modulation by NO via a cGMP-dependent mechanism that requires K(ATP) channel activation. Based on the similar findings in soleus and EDL muscles, fibre type does not appear to determine the innate vascular response to alpha(1)- or alpha(2)-adrenoceptor activation.
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PMID:{alpha}-Adrenoceptor constrictor responses and their modulation in slow-twitch and fast-twitch mouse skeletal muscle. 1561 69

Excess and deficit of growth hormone (GH) both affect cardiac architecture as well as its function. To date, experimental and clinical studies have reported that GH has an inotropic effect on animal and human heart, however, it remains controversial whether GH is applicable to the treatment for the patients with chronic heart failure. Also, the mechanism by which GH exerts these biological effects on the heart is not well understood. In this study, we attempted to specify the genes regulated by GH in the heart of spontaneous dwarf rat using a microarray analysis. We found that soluble forms of guanylate cyclase, cofilin1, and thymosin beta4 mRNA were up-regulated in the heart by GH treatment. On the other hand, acyl-CoA synthetase, aldosterone receptor, myosin regulatory light chain, troponin T, laminA, and beta-actin mRNA were down-regulated. These results suggest GH regulates essential molecules that regulate structural, contractile, remodeling, and regenerative functions. Collectively, our data indicate a new integrative understanding for the biological effects of GH on cardiac function.
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PMID:Gene expression profile in the heart of spontaneous dwarf rat: in vivo effects of growth hormone. 1641 79