Relaxation Response to Pinacidil and Diazoxide in the Mouse Isolated Distal Colon

Lebrun, Philippe; Fontaine, Jeanine

doi:10.1159/000138634

Cited by 10 publications

(4 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…"~ In mouse distal colon, spontaneous contractile activity was inhibited by pinacidil and diazoxide, respective IC50 values being 6 and 100 pM. 425 In guinea pig taenia caeci, cromakalim (0.3-3 pM) relaxed contractions induced by 10 mM KCl or carba~hol.~' Similar findings were obtained with pinacidil and nicorandil against 30 mM KCl contractions and, interestingly, both drugs fully relaxed contractions due to 100 mM KCl.421 When caffeine was employed to contract the tissue, presumably by release of intracellular Ca2 + from stores, pinacidil and nicorandil had an inhibitory effect. After saponin treatment to permeabilize the cell membrane in taenia caeci, Ca2+-induced contractions were not inhibited by pinacidil (300 pM), although trifluoperazine and W-7 (protein kinase C inhibitors) were active.…”

Section: Gastrointestinal Smooth Musclementioning

confidence: 99%

Potassium channel activator drugs: Mechanism of action, pharmacological properties, and therapeutic potential

Longman¹,

Hamilton

1992

Medicinal Research Reviews

127

View full text Add to dashboard Cite

Section: Gastrointestinal Smooth Musclementioning

confidence: 99%

Potassium channel activator drugs: Mechanism of action, pharmacological properties, and therapeutic potential

Longman¹,

Hamilton

1992

Medicinal Research Reviews

127

View full text Add to dashboard Cite

“…Published reports on the actions of K + channel modulating agents on gastrointestinal smooth muscle include studies on guinea-pig intestine (Weir & Weston 1986;Schwo $ rer & Kilbinger 1989;Zini et al 1991), rat stomach (Lefebvre & Horacek 1992) and rat ileum (Davies et al 1991(Davies et al , 1996. Only one report on the eOE ects of these agents in murine gastrointestinal tissue is available (Lebrun & Fontaine 1990). Because of the increasing importance of mice in transgenic studies, the mouse small intestine was chosen for this study, in which the eOE ects of a variety of K + channel modulators were characterised in-vitro.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the effects of potassium channel modulating agents on mouse intestinal smooth muscle

Yeung

McCurrie

Wood

2002

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

The actions of agents which modulate ATP-sensitive potassium (K(ATP)) channels in excitable cells were investigated in an in-vitro preparation of mouse ileum from which the mucosa was removed. A range of potassium channel openers of diverse structure, cromakalim (0.1-100 microM), pinacidil (0.1-200 microM) and its analogue P1060 (0.1-200 microM), SDZ PCO400 ((-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile) (0.3-60 microM), caused concentration-related reduction in twitch height of electrical field stimulated ileum. P1060 and SDZ PCO400 were the most potent agents; diazoxide (0.1-100 microM) was without effect. The order of inhibitory potency, based on EC50 values (concentration of a relaxant producing 50% of the maximum inhibition of twitch) was: P1060 = SDZ PCO400 > cromakalim > pinacidil. The relaxant effect of the potassium channel openers was antagonised by the sulfonylureas glibenclamide (0.1-1.0 microM) and glipizide (3-30 microM) but the nature of the antagonism differed. Antagonism of P1060 and SDZ PCO400 by glibenclamide appeared to be competitive whereas the antagonism of relaxation induced by cromakalim and pinacidil was apparently not competitive. Both phentolamine (1-10 microM) and tolbutamide (100-300 microM) showed competitive antagonism of the actions of pinacidil while yohimbine (1-20 microM) did not antagonise relaxation and appeared to have actions at sites other than the K(ATP) channel in this preparation. The relative effectiveness of the antagonists on pinacidil-induced relaxation was found to be: glibenclamide> phentolamine > tolbutamide > yohimbine, which is in agreement with studies in other tissues. The results show that many structurally diverse potassium channel openers are potent relaxants of mouse ileum. These observations are consistent with the existence of ATP-dependent K+ channels in murine intestinal muscle which, however, differ somewhat in properties from those reported for vascular muscle and pancreatic beta-cells.

show abstract

“…Such a difference could conceivably reflect an improved secretory efficiency of the B-cell following the 48 hours of in vivo secretory inactivity. However, the parallel changes in perfusion pressure and insulin output rather suggest that the functional behaviour of both B-cells and smooth muscle cells during perfusion results from a rebound closure of ATP-sensitive K + channels after removal of the pancreas from the diazoxide-treated rats and, hence, upon relief from the diazoxide-induced opening of the same channels {Cook 1988; Lebrun and Fontaine 1990). In this perspective, the finding that D-glucose caused a further increase of the perfusion pressure suggests that glucose may also control the gating of K + channels in the sensitized smooth muscle cells of diazoxide-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Attenuated Anomeric Difference of Glucose-Induced Insulin Release in the Perfused Pancreas of Diazoxide-Treated Rats

Leclercq‐Meyer¹,

Marchand²,

Malaisse³

1991

Horm Metab Res

View full text Add to dashboard Cite

Mild hyperglycemia was induced in normal rats by oral administration of both diazoxide and D-glucose. After 48 hours of such a treatment, the insulin and glucagon secretory responses of the perfused pancreas to alpha- and beta-D-glucose (3.3 mM) were examined in the presence of 10.0 mM L-leucine. The output of insulin, but not that of glucagon, and the perfusion pressure were higher in treated than control rats. The alpha-anomer of D-glucose was a more potent insulin secretagogue than beta-D-glucose in both control and treated rats. However, the alpha/beta ratio in insulin output was twice higher in control than treated rats. By analogy with other experimental models of diabetes, the attenuation in the anomeric difference of glucose-stimulated insulin output in the treated rats could reflect an altered secretory response to alpha- rather than beta-D-glucose. These findings suggest that hyperglycemia provokes, as a function of its severity and duration, first attenuation and then suppression, if not inversion, of the anomeric preference for alpha-D-glucose in insulin release. They are also compatible with the hypothesis that the anomeric malaise, associated with B-cell glucotoxicity, is caused by a progressive accumulation of glycogen in this cell.

show abstract

Relaxation Response to Pinacidil and Diazoxide in the Mouse Isolated Distal Colon

Cited by 10 publications

References 14 publications

Potassium channel activator drugs: Mechanism of action, pharmacological properties, and therapeutic potential

Potassium channel activator drugs: Mechanism of action, pharmacological properties, and therapeutic potential

Characterisation of the effects of potassium channel modulating agents on mouse intestinal smooth muscle

Attenuated Anomeric Difference of Glucose-Induced Insulin Release in the Perfused Pancreas of Diazoxide-Treated Rats

Contact Info

Product

Resources

About