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)

The discovery of the atrial natriuretic factor (ANF) has opened a new field in modern biology. After rapid isolation and identification of this new peptide from atrial granules, it is now evident that this new hormone has a wide variety of actions with general implication in the control of vascular tone, sodium and water balance, hormonal secretion as well as neuronal functions. The major mode of action of this hormone is transmitted via its interaction with a membrane enzyme, particulate guanylate cyclase, leading to increases of cGMP levels. This nucleotide is a faithful marker of ANF action correlating with all functions ascribed to ANF up to date. Significant increases of ANF as well as of cGMP have been discovered in heart and renal failure, secondary hypertension and other states with altered salt-water balance, impairment of heart function and particularly increase of atrial pressure. The increases of levels and relative inefficiency of increased ANF have to be carefully interpreted in face of increased levels of cGMP. It can be expected that new pharmacological developments will occur in this area issuing from both our increasing knowledge concerning the peripheral mode of action of this hormone, its physiological implications as well as its pharmacological effectiveness in diseases with altered salt-water balance, cardiac function and blood pressure disregulation.
 ...
PMID:[Physiological and physiopathological aspects of the atrial natriuretic factor]. 288 82

Isatin (1H-indole-2,3 dione) is an endogenous compound that may act as a physiological regulator of muscle contraction by reducing cGMP production by inhibition of guanylyl cyclase (GC) activity. Intracellular cGMP levels can regulate the contractile response of smooth muscle. Therefore, in the present study we investigated the effects of seven novel carbamate derivatives of isatin, namely C1-C7, on the contractility of aortic rings from Wistar rats. Carbamates C1 and C6 most effectively promoted endothelium-dependent relaxation of aortic rings pretreated with 10 micromol/L phenylephrine (PE) to induce contraction. The concentration of the C1 and C6 carbamates necessary to reduce PE-induced aortic contraction by 50% (IC(50)) was 5.6 +/- 1.0 and 48.4 +/- 3.4 micromol/L, respectively. Carbamate derivative-induced vasodilation required an intact endothelium, which is responsible for nitric oxide (NO) release. Pretreatment of rings with 100 micromol/L naloxone or 10 micromol/L atropine prevented the C1- and C6-mediated vascular relaxation, indicating that the vasodilatory activity was dependent on the activation of opioid or muscarinic receptors, respectively. The results of our studies provide insights into the role of novel carbamates in the regulation of vascular tone. Carbamates could stimulate NO synthesis, which induces vasodilation primarily by stimulation of GC and cGMP production. Taken together, our findings suggest that carbamate derivative-induced vasodilation may be considered an alternative treatment for primary and/or secondary hypertension.
 ...
PMID:Vasodilatory activity of novel carbamate derivatives of isatin. 1850 49