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 purpose of this study was to investigate the interactions of compounds structurally related to imidazoline at K+ channels located in the rat portal vein. Nicorandil, a K+ channel activator, dose dependently inhibited spontaneous contractions of the isolated rat portal vein. Glibenclamide (0.1-1 microM), an ATP-sensitive K+ channel blocker, competitively antagonized the response to nicorandil, whereas methylene blue (10 microM), a guanylate cyclase inhibitor, did not. Phentolamine, antazoline, tolazoline, and midaglizole also shifted the dose-response curve for nicorandil to the right in the dose range of 1-100 microM. The rank order of potency was glibenclamide much greater than phentolamine = antazoline = midaglizole greater than tolazoline. In contrast, clonidine, idazoxan, imidazole, 1-benzylimidazole, and yohimbine were ineffective. In addition, cromakalim (1-100 nM), a selective K+ channel activator, also inhibited spontaneous contractions of the rat portal vein, and this effect was antagonized by phentolamine in a similar way to that found with nicorandil. These results suggest that some 2-substituted imidazolines, including phentolamine, possibly act as K+ channel blockers, like glibenclamide, in vascular smooth muscle.
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PMID:Effects of imidazoline-related compounds on the mechanical response to nicorandil in the rat portal vein. 139 88

In this study the role of the endothelium was evaluated in the relaxation of rat aortic rings induced by a number of alpha adrenergic antagonists. Phentolamine, a nonselective alpha adrenergic antagonist, relaxed rat aortic rings that were previously contracted with an EC80 dose of phenylephrine, in a concentration-dependent manner. Removal of the endothelium significantly reduced the sensitivity but not the amplitude of the response. The presence of endothelium also enhanced the vascular relaxation induced by yohimbine, a specific alpha-2 adrenergic antagonist (10(-8)-10(-6) M), and by prazosin, a specific alpha-1 adrenergic antagonist (10(-11)-10(-9) M). Both methylene blue (10(-5) M), an inhibitor of soluble guanylate cyclase, and eicosatetraynoic acid (3.2 X 10(-5) M) blocked the endothelial augmentation of vascular relaxation to phentolamine. Vessels precontracted with potassium chloride were slightly relaxed by phentolamine (10(-8)-10(-6) M) only with the endothelium was intact. Both methylene blue and eicosatetraynoic acid also inhibited the response to phentolamine in the intact vessels precontracted with potassium chloride. Prazosin (10(-9)-10(-7) M) and yohimbine (10(-8)-10(-6) M), unlike phentolamine, failed to induce relaxation in potassium chloride-precontracted vessels. When the vessels were precontracted with the thromboxane analog U46619 none of the three alpha antagonists induced vascular relaxation. These results indicate that the endothelium has a significant role in promoting relaxation induced by the three alpha adrenergic antagonists tested.
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PMID:Endothelial potentiation of relaxation response to phentolamine in rat thoracic aorta. 283 42

1. Makatoxin I (MkTx I) is a new toxin purified from the venom of the scorpion Buthus martensi Karsch. Contractile (excitatory, adrenergic) and relaxant (inhibitory, nitrergic) responses of the rat isolated anococcygeus muscle (Acm) to MkTx I were investigated. 2. MkTx I (0.28 microM) produced a rapid and very marked rise in the tone of the Acm which then gradually wanted to the control baseline. Phentolamine (5 microM), guanethidine (5 microM), tetrodotoxin (2 microM) and reserpine pretreatment in vivo (5 mg kg-1 s.c. at 24 hr and 5 mg kg-1 i.p. at 3 h) completely blocked the contractile responses of the Acm to MkTx I. The responses to noradrenaline (NA) were blocked by phentolamine, but were potentiated by guanethidine. 3. MkTx I (0.28 microM) also marked and rapidly relaxed the tone of the carbachol (CCh; 3 microM), precontracted Acm. The addition of sodium nitroprusside (SNP; 1 microM) also produced a marked and rapid relaxation of the Acm. TTx (2 microM) or NG-nitro-L-arginine methylester (L-NAME, 50 microM) markedly inhibited the relaxant responses of the Acm to field stimulation (FS) as well as to MkTx I, but not the responses to SNP. 4. Therefore, the contractile responses of the rat anococcygeus muscle to MkTx I can be attributed to the release of transmitter NA on postjunctional alpha-adrenoceptors, whereas the relaxant responses of the Acm to MkTx I involve the release of nitric oxide as the neurotransmitter which, presumably, results in the activation of the enzyme guanylate cyclase leading to relaxation of the muscle.
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PMID:Adrenergic and nitrergic responses of the rat isolated anococcygeus muscle to a new toxin (makatoxin I) from the venom of the scorpion Buthus martensi Karsch. 923 83

The aim of this study was to clarify if phentolamine has proven effects on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine involving the ATPsensitive K(+) channels and adrenergic receptor. The actions of phentolamine on pacemaker activities were investigated using whole-cell patch-clamp technique and intracellular Ca(2+) analysis at 30 degrees C in cultured mouse intestinal ICC. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. Treatment with phentolamine reduced the frequency and amplitude of the pacemaker currents and increased the resting outward currents. Moreover, under current clamping (I = 0), phentolamine hyperpolarized the ICC membrane and decreased the amplitude of the pacemaker potentials. We also observed that phentolamine inhibited spontaneous [Ca(2+)](i) oscillations in ICC. The alpha-adrenergic drugs prazosin, yohimbine, methoxamine, and clonidine had no effect on ICC intestinal pacemaker activity and did not block phentolamine-induced effects. Phentolamine-induced effects on the pacemaker currents and the pacemaker potentials were significantly inhibited by ATP sensitive K(+) channel blocker glibenclamide, but not by TEA, apamin, or 4-aminopyridine. In addition, the NO synthase inhibitor, L-NAME and the guanylate cyclase inhibitor, ODQ were incapable of blocking the phentolamine-induced effects. These results demonstrate that phentolamine regulates the pacemaker activity of ICC via ATP-sensitive K(+) channel activation. Phentolamine could act through an adrenergic receptor- and also through NO-independent mechanism that involves intracellular Ca(2+) signaling.
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PMID:Phentolamine inhibits the pacemaker activity of mouse interstitial cells of Cajal by activating ATP-sensitive K+ channels. 2036 15