Dopamine D2‐like receptor‐mediated opening of K+ channels in opossum kidney cells
7
Citation
52
Reference
10
Related Paper
Citation Trend
Abstract:
This study examined the effects of dopamine D 1 ‐ and D 2 ‐like receptor activation upon basolateral K + ( I K ) currents and changes in membrane potential in opossum kidney (OK) cells. The addition of amphotericin B (3 μg ml −1 ) to the apical side resulted in a rapid increase in I K , this effect being markedly inhibited by the addition of the K + channel blockers barium chloride (1 m M ) or glibenclamide (10 μ M ), but not apamin (1 μ M ). The K + channel opener pinacidil increased the amphotericin B‐induced I K . The selective D 2 ‐like receptor agonist quinerolane increased, in a concentration dependent manner (EC 50 =136 n M ), I K across the basolateral membrane, this effect being abolished by pre‐treatment with pertussis toxin (PTX), S‐sulpiride (selective D 2 ‐like receptor antagonist) and glibenclamide. The selective D 1 ‐like receptor agonist SKF 38393 did not change I K . Both H‐89 (PKA inhibitor) and chelerythrine (PKC inhibitor) failed to prevent the stimulatory effect of quinerolane upon I K . Quinerolane did not change basal levels of cyclic AMP and also failed to affect the forskolin‐induced increase in cyclic AMP levels. The stimulation of D 2 ‐like receptor was associated with a rapid hyperpolarizing effect, whereas D 1 ‐like receptor activation was accompanied by increases in cell membrane potential. The hyperpolarizing effect of quinerolane (EC 50 =129 n M ) was prevented by pre‐treatment with PTX, S‐sulpiride and glibenclamide. It is concluded that stimulation of dopamine D 2 ‐like, but not D 1 ‐like, receptors coupled to PTX‐sensitive G proteins of the G i/o class produce membrane hyperpolarization through opening of K ATP channels. British Journal of Pharmacology (2003) 138 , 968–976. doi: 10.1038/sj.bjp.0705125Keywords:
Apamin
Sulpiride
Sulpiride
Dopamine antagonist
Cite
Citations (27)
To asses the efficacy of combination therapy of glibenclamide and Kelening in treating the non-insulin dependent diabetes mellitus (NIDDM).Sixty-five patients with NIDDM were randomly divided into two groups. One group was treated with both glibenclamide and Kelening, the other with glibenclamide alone.After treatment for 12 weeks, the levels of fasting blood glucose (FBG), postprandial blood glucose (PBG) and HBAIC were reduced significantly in glibenclamide-Kelening group. In both groups, the degree dropped of the levels of FBG were almost the same, but the levels of PBG and HBAIC in glibenclamide-Kelening group were reduced more significantly than those in glibenclamide group, and the incidence of hyperinsulinemia had dropped considerably.Glibenclamide in combination with Kelening in the treatment of NIDDM is more effective and less toxic, and the combination may reduce the dosage of glibenclamide in NIDDM.
Hyperinsulinemia
Cite
Citations (2)
Sulpiride
Dopamine antagonist
Cite
Citations (6)
Glibenclamide Block of K ATP Channels. Introduction: The mechanism by which glibenclamide inhibits K ATP channel activity has been examined in membrane patches from isolated rat ventricular cells. Methods and Results: Inside‐out patches were exposed to zero, or low, [ATP] to activate K ATP channels. Glibenclamide did not affect single channel conductance, but reversibly reduced channel open probability from either side of the membrane. Internal (cytoplasmic) glibenclamide inhibited with half‐maximal inhibitory [glibenclamide] = 6 μM, Hill coefficient = 0.35. Complete channel inhibition was not observed, even at 300 μM [glibenclamide]. The response to step increases of internal [glibenclamide] could be resolved into two phases of channel inhibition (t 1/2, fast , < 1 sec, t 1/2, slow = 10.5 ± 0.9 sec, n = 8). Step decrease of [glibenclamide] caused a single resolvable phase of reactivation (t 1/2 = 20.4 ± 0.7 sec, n = 16). Channel inhibition by internal glibenclamide could be relieved by ADP, but only in the presence of Mg 2+ . Conclusion: Glibenclamide can inhibit K ATP channels from either side of the membrane, with block from one side being competitive with block from the other. Internal MgADP antagonizes the blocking action of glibenclamide. Glibenclamide inhibition of cardiac K ATP channels differs quantitatively and qualitatively from the inhibition of pancreatic K ATP channels.
Mechanism of Action
Cite
Citations (49)
Different doses of glibenclamide and of 4-transhydroxy-glibenclamide (main metabolite in man) were administered i.p. to rats and blood glucose was measured. The comparison of the doses capable of producing a 30% decrease of the glycemia shows that 4-trans-hydroxy-glibenclamide is about 6.5 times less potent than glibenclamide in our experimental conditions.
Cite
Citations (17)
The effects of d-Sulpiride (25 mg i.v.) and 1-Sulpiride (25 mg i.v.) administration in the control of arterial blood pressure (ABP) and PRL-GH secretion have been analyzed in five normal male volunteers. It was observed a quite different action on ABP, 1-Sulpiride causing a long lasting hypotension and d-Sulpiride a short-lived hypertension. The correlation between ABP, heart rate and PRL-GH levels suggests a probable central cation for 1-Sulpiride and a possible peripheral action for d-Sulpiride effects on ABP.
Sulpiride
Cite
Citations (0)
Cite
Citations (4)
Glycemia and insulinemia in rat blood samples have been determined at different times before and after administration of glibenclamide, PGE1, glibenclamide and PGE1, glibenclamide and glucose, PGE1 and glucose, and glibenclamide, PGE1 and glucose. PGE1 led to a partial inhibition of glibenclamide induced insulin release, with and without glucose administration, but a total inhibition did not occur. The inhibitory action of PGE1 on insulin secretion was also reflected on the glycemia curves. Defects in insulin release in diabetes could be due in part to an excessive production of PGs, that involve a failure in the beta-cells to respond to glucose signals. The present paper shows that glibenclamide secretory action was not cancelled out by PGE1. These results could explain the availability of glibenclamide in the treatment of diabetes mellitus.
Cite
Citations (1)
Although some studies indicate that sulpiride (an atypical neuroleptic drug) increases body weight in female rodents after long-term administration, this action is less clear in males. In this study, we examined the effect of three doses of sulpiride (40, 60 or 80 mg/kg, ip) or physiological saline, chronically administered during 9 consecutive days, on body weight in the OF.1 strain of adult male mice. All animals were housed in transparent plastic cages during four weeks (non-drug period) and weighted weekly. During the drug period, sulpiride was administered once daily for 9 days and body weights measured. Results showed that sulpiride did not vary body weight after chronic administration, suggesting that the action of some neuroleptics on body weight might be a sex-dependent phenomenon.
Sulpiride
Drug Administration
Cite
Citations (2)
Effects of apamin on rat sympathetic neurones were investigated by means of intracellular and extracellular recording. Apamin (50 nM) significantly shortened the after‐hyperpolarization (AH) following the spike evoked by current injection and slightly decreased its peak amplitude without affecting the time course of the spike. The AH following the synaptically‐evoked spike was also blocked by apamin. This effect was dose‐and time‐dependent (ID 50 estimated by extracellular recording approximately 15 nM, 20 min after application) and poorly reversible. Transmission of a single volley was not affected by 50 nM apamin. Though a long depolarizing current caused one or two spikes in the cell, greater repetitive firing was observed in the presence of apamin. Spontaneous repetitive firing, however, was not observed except for anodal‐break spikes. Resting potential and input membrane resistance were essentially unchanged by apamin. The maximum rate of rise of the Ca spike was not decreased by 50 nM apamin but the duration of the spike was lengthened by 60%. The AH following the Ca spike was also blocked by apamin. These results suggest that apamin suppressed the slow AH without any inhibition of the Ca flux into the cell and is useful as a blocker of G K(Ca) in the rat sympathetic neurone.
Apamin
Sympathetic nervous system
Cite
Citations (124)