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)

Bumetanide reduced basal tension of resting carotid arteries as well as tonic contraction elicited by 36 mM of KCl, KNO3 and 0.1 mM norepinephrine but had little effect on phasic response to norepinephrine and angiotensin II. Bumetanide was much more active against norepinephrine than KCl, KNO3 and its effect was not reduced by propranolol. These findings establish a distinction between bumetanide and the Ca antagonists, which do not affect basal tension but selectively inhibit potassium (K+) contracture. On the contrary, this compound resembles the nitrocompounds in that vascular relaxation does not require the integrity of endothelium but is abolished by methylene blue. These two common traits support the view that the increased synthesis of cyclic GMP secondary to guanylate cyclase activation may be directly involved in the vasodilating properties of the drug.
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PMID:Vascular relaxing effects of bumetanide. 258 95

Intestinal salt and fluid secretion is stimulated by Escherichia coli heat-stable enterotoxins (ST) through activation of a membrane guanylate cyclase found in the intestine. Guanylin is an endogenous intestinal peptide that has structural similarity to the bacterial peptides. Synthetic preparations of guanylin or E. coli ST 5-17 stimulated Cl- secretion in T84 cells cultured on semipermeable membranes as measured by increases in short circuit current (Isc). The guanylin/ST receptors appeared to be on the apical surface of T84 cells, since addition of guanylin to the apical, but not basolateral, reservoir stimulated Isc. Bumetanide added to the basolateral side effectively inhibited the Isc responses of T84 cells to either guanylin or ST 5-17. Guanylin appeared to be about one-tenth as potent as ST in stimulating transepithelial Cl- secretion. Guanylin and E. coli ST 5-17 both caused massive (> 1,000-fold) increases in cGMP levels in T84 cells, but guanylin was less potent than ST. Both peptides fully inhibited the binding of 125I-ST to receptor sites on intact T84 cells. The radioligand binding data obtained with guanylin or ST 5-17 best fit a model predicting two receptors with different affinity for these ligands. The Ki values for guanylin were 19 +/- 5 nM and 1.3 +/- 0.5 microM, whereas the Ki values for ST 5-17 were 78 +/- 38 pM and 4.9 +/- 1.4 nM. We conclude that guanylin stimulated Cl- secretion via the second messenger, cGMP, in T84 human colon cells. At least two guanylin receptors with different affinities for these ligands may exist in the cultured T84 cells. It may be postulated that guanylin is an endogenous hormone that controls intestinal Cl- secretion by a paracrine mechanism via cGMP and that E. coli ST stimulates Cl- secretion by virtue of an opportunistic mechanism through activation of guanylin receptors.
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PMID:Guanylin stimulation of Cl- secretion in human intestinal T84 cells via cyclic guanosine monophosphate. 839 Apr 80