The Sulphonylurea Receptor May Be an Atp-Sensitive Potassium Channel

Sturgess, Nicholas C.; Cook, Daniel L.; Ashford, M. L. J.; Hales, C. N.

doi:10.1016/s0140-6736(85)90403-9

Cited by 514 publications

(288 citation statements)

References 10 publications

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“…We tested the hypothesis that sildena®l may exert its neuromodulatory e ects by activation of K + channels in the human vas deferens. Our results show that glibenclamide, a blocker of ATP-sensitive K + channels (Sturgess et al, 1985), and apamin, a blocker of small-conductance Ca 2+ -activated K + channels (Murphy & Brayden, 1995), failed to alter the inhibition caused by sildena®l on neurogenic contractions. On the other hand, TEA, a nonspeci®c K + channel blocker (Benham et al, 1985), iberiotoxin, an inhibitor of large conductance Ca 2+ -activated K + channels (Galvez et al, 1989) and charybdotoxin, an inhibitor of both large and intermediate conductance Ca 2+ -activated K + channels (Garcia et al, 1995) inhibited the e ects of sildena®l on electrical ®eld stimulation.…”

Section: Resultsmentioning

confidence: 66%

Inhibition of neuroeffector transmission in human vas deferens by sildenafil

Medina

Segarra

Torondel

et al. 2000

British J Pharmacology

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Sildena®l (0.1 ± 30 mM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 ± 100 mM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 ± 100 mM) had no e ect on neurogenic contractions. The inhibition induced by sildena®l was not modi®ed by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) (1 ± 30 mM) but it was abolished by the K + channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 mM) and charybdotoxin (0.1 mM). Sildena®l, zaprinast and SNP did not a ect the contractions induced by noradrenaline. SNP (10 mM) caused elevation of cyclic GMP levels that was potentiated by sildena®l (10 mM) and zaprinast (100 mM). ODQ (10 mM) inhibited the increase in cyclic GMP. Sildena®l inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca 2+ -activated K + channels.

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Section: Resultsmentioning

confidence: 66%

Inhibition of neuroeffector transmission in human vas deferens by sildenafil

Medina

Segarra

Torondel

et al. 2000

British J Pharmacology

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“…The hypoglycemic sulfonylureas, a family of drugs of particular interest in the management of diabetes meUitus [1], display specific membranebound receptors both at the level of the pancreatic B-cells [2,3] and in the central nervous system [4,5], a receptor which is linked to an ionic channel effector [6][7][8][9]. This led us to suggest that this biologically relevant receptor is probably the natural recognition system of an endogenous ligand [5].…”

Section: Discussionmentioning

confidence: 99%

“…As far as the sulfonylurea receptor is concerned, it has been clearly established that the binding site is specific for the different hypoglycemic sulfonylureas with respective affinities in close relation with their in vivo biological activities [2][3][4][5]. Furthermore, an ionic channel is suspected to be the effector system linked to the sulfonylurea binding site, although some discrepancies appeared in the literature concerning its exact type, either an ATP-dependent K + [6,7], a Ca2+-dependent K + [8] or a voltage-dependent Ca 2+ [9] channel. Thus, the sulfonylurea receptor Correspondence address: A. Virsolvy-Vergine, Centre CNRS-INSERM de Pharmacologie-Endocrinologie, Rue de la Cardonille, 34094 Montpellier Cedex 2, France displays all the characteristics of a biologically relevant receptor for a still unknown endogenous ligand [5].…”

Section: Introductionmentioning

confidence: 99%

An endogenous ligand for the central sulfonylurea receptor

et al. 1988

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“…Glibenclamide, an inhibitor of ATP-sensitive K ϩ channels, 25 apamin, a specific blocker of small conductance Ca 2ϩ -activated K ϩ channels 26 or iberiotoxin, a specific blocker of large conductance Ca 2ϩ -activated K ϩ channels 27 had no effects on adrenergic-mediated contractions of the human vas deferens. Thus, large and small conductance Ca 2ϩ -activated K ϩ channels and ATP-sensitive K ϩ channels do not appear to be activated in association with adrenergic neurotransmitter in human vas deferens.…”

Section: Commentmentioning

confidence: 99%

Modulation of Adrenergic Responses of Human Vas Deferens by K+ Channel Inhibitors

Medina

Segarra

Mauricio

et al. 2010

Urology

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OBJECTIVESThe present study was designed to evaluate the role of K ϩ channels in the adrenergic responses of human vas deferens as well as the intervention of dihydropyridine-sensitive Ca 2ϩ channels on modulation of adrenergic responses by K ϩ channel inhibitors. METHODSRing segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of K ϩ channel blockers on neurogenic and norepinephrine-induced contractile responses. RESULTSAddition of tetraethylammonium (TEA, 10 Ϫ3 M), a nonspecific K ϩ channel blocker, or charybdotoxin (10 Ϫ7 M), a nonselective inhibitor of large-and intermediate-conductance Ca 2ϩ -activated K ϩ channel, increased the contractile responses to norepinephrine and electrical field stimulation-induced contractions (P Ͻ .01), whereas iberiotoxin (10 Ϫ7 M), a selective blocker of large-conductance Ca 2ϩ -activated K ϩ channels, apamin (10 Ϫ6 M), a blocker of small-conductance Ca 2ϩ -activated K ϩ channels, or glibenclamide (10 Ϫ5 M), an inhibitor of ATP-sensitive K ϩ channels, were without effect. TEA-and charybdotoxin-induced potentiation of contractions elicited by electrical field stimulation and norepinephrine was blocked by L-type Ca 2ϩ channel blocker nifedipine (10 Ϫ6 M). CONCLUSIONSThe results suggest that charybdotoxin-sensitive, but iberiotoxin-insensitive, K ϩ channels are activated by stimulation with norepinephrine and electrical field stimulation to counteract the adrenergic-induced contractions of human vas deferens. Thus, inhibition of these channels increases significantly the contraction, an effect that appears to be mediated by an increase in Ca 2ϩ entry through L-type voltage-dependent Ca 2ϩ channels. UROLOGY 76: 1518.e7-1518.e12, 2010.

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The Sulphonylurea Receptor May Be an Atp-Sensitive Potassium Channel

Cited by 514 publications

References 10 publications

Inhibition of neuroeffector transmission in human vas deferens by sildenafil

Inhibition of neuroeffector transmission in human vas deferens by sildenafil

An endogenous ligand for the central sulfonylurea receptor

Modulation of Adrenergic Responses of Human Vas Deferens by K+ Channel Inhibitors

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