GLORIA

GEOMAR Library Ocean Research Information Access

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Some degree of overlap exists between the K+-channels opened by cromakalim and those opened by minoxidil sulphate in rat isolated aorta (1991)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 344 (1991), S. 351-359 
    Details
    ISSN: 1432-1912
    Keywords: Cromakalim ; Minoxidil sulphate ; K+ channel opener ; Glibenclamide 42K+/86Rb+ efflux
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the K+ channel opening drugs minoxidil sulphate and cromakalim, on 42K+ and 86Rb+ efflux and on vasorelaxation in rat isolated aorta, were compared. In rat aortic rings precontracted with noradrenaline (100 nmol/l), minoxidil sulphate and cromakalim concentration-dependently inhibited induced tension by up to 90%, with pD2 values of 7.35±0.1 and 7.17±0.1, respectively. Glibenclamide (300 nmol/l), produced 2200- and 19-fold rightward shifts in the concentration-relaxation curves to minoxidil sulphate and cromakalim, respectively, without an effect on the maximum relaxation. Both minoxidil sulphate and cromakalim increased the efflux of 42K+ and 86Rb+ from aorta in a concentration-dependent manner, with midpoints in the µmol/l range; the maximum efflux induced by minoxidil sulphate being approximately one tenth of that induced by cromakalim. The ratio of stimulated 86Rb+/42K+ efflux increased from 0.22 to 0.48 with increasing cromakalim concentrations, but was approximately constant (≈0.39) when the minoxidil sulphate concentration was varied. In the presence of minoxidil sulphate, the effects of cromakalim on 42K+ and 86Rb+ efflux were inhibited in a concentration-dependent manner, by up to 60%. In the continuing presence of cromakalim (300 nmol/l), minoxidil sulphate (10 µmol/l)-induced increases in 42K+ and 86Rb+ efflux were inhibited by 45%, whereas conditioning with cromakalim (1 µmol/l) inhibited the 86Rb+ efflux stimulated by additional superfusion of cromakalim (1 µmol/l) by 85%. Glibenclamide inhibited minoxidil sulphate (10 µmol/l)- and cromakalim (1 µmol/l)-induced increases in 42K+ and 86Rb+ efflux in a concentration-dependent manner with IC50 values of approximately 80 nmol/l. In conclusion, the efflux data suggest that considerable overlap exists between the channels opened by minoxidil sulphate and those opened by cromakalim in rat aorta. Minoxidil sulphate has a weak efficacy as a K+ channel opener, and may act to open a homogeneous population of K+ channels. In contrast, the actions of cromakalim (≥1 µmol/l) are associated with large increases in tracer efflux, which are probably mediated via a heterogeneous population of K+ channels. However, only a small proprtion of this induced efflux appears to be required for relaxation. The differential inhibition by glibenclamide of the vasorelaxant effects of minoxidil sulphate and cromakalim may result from (a) the partial agonist properties of minoxidil sulphate in opening K+ channels and/or (b) additional mechanisms of vasorelaxation, which differ in their sensitivity to glibenclamide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00183011
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    ATP-sensitive K+ channels in the kidney (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 213-225 
    Details
    ISSN: 1432-1912
    Keywords: Key words ATP-sensitive K+ channels (KATP channels) ; Sulphonylureas ; KATP channel openers ; Renal KATP ; channel blockers ; Eukalemic diuresis ; Renin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract ATP-sensitive K+ channels (KATP channels) form a link between the metabolic state of the cell and the permeability of the cell membrane for K+ which, in turn, is a major determinant of cell membrane potential. KATP channels are found in many different cell types. Their regulation by ATP and other nucleotides and their modulation by other cellular factors such as pH and kinase activity varies widely and is fine-tuned for the function that these channels have to fulfill. In most excitable tissues they are closed and open when cell metabolism is impaired; thereby the cell is clamped in the resting state which saves ATP and helps to preserve the structural integrity of the cell. There are, however, notable exceptions from this rule; in pancreatic β-cells, certain neurons and some vascular beds, these channels are open during the normal functioning of the cell. In the renal tubular system, KATP channels are found in the proximal tubule, the thick ascending limb of Henle’s loop and the cortical collecting duct. Under physiological conditions, these channels have a high open probability and play an important role in the reabsorption of electrolytes and solutes as well as in K+ homeostasis. The physiological role of their nucleotide sensitivity is not entirely clear; one consequence is the coupling of channel activity to the activity of the Na-K-ATPase (pump-leak coupling), resulting in coordinated vectorial transport. In ischemia, however, the reduced ATP/ADP ratio would increase the open probability of the KATP channels independently from pump activity; this is particularly dangerous in the proximal tubule, where 60 to 70% of the glomerular ultrafiltrate is reabsorbed. The pharmacology of KATP channels is well developed including the sulphonylureas as standard blockers and the structurally heterogeneous family of channel openers. Blockers and openers, exemplified by glibenclamide and levcromakalim, show a wide spectrum of affinities towards the different types of KATP channels. Recent cloning efforts have solved the mystery about the structure of the channel: the KATP channels in the pancreatic β-cell and in the principal cell of the renal cortical collecting duct are heteromultimers, composed of an inwardly rectifying K+ channel and sulphonylurea binding subunit(s) with unknown stoichiometry. The proteins making up the KATP channel in these two cell types are different (though homologous), explaining the physiological and pharmacological differences between these channel subtypes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171051
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Ba2+ differentially inhibits the Rb+ efflux promoting and the vasorelaxant effects of levcromakalim and minoxidil sulfate in rat isolated aorta (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1995), S. 86-93 
    Details
    ISSN: 1432-1912
    Keywords: Levcromakalim ; Minoxidil sulfate ; Ba2+ ; Glibenclamide ; Tedisamil ; ATP-sensitive K+ channels ; K+ channel opening ; Vasorelaxation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The K+ channel openers activate ATP-sensitive K+ channels (KATP) in vascular smooth muscle and induce relaxation. In this study, the relationship between these two effects was examined in rings of rat aorta using levcromakalim and minoxidil sulfate as the openers and Ba2+ as the K+ channel blocker; K+ channel opening was assessed by determining the rate constant of 86Rb+ efflux from the preparation. Ba2+ inhibited the 86Rb+ efflux stimulated by levcromakalim in a noncompetitive manner with an IC50 value of 29 μM and a Hill-coefficient of 1.2. At concentrations 〉 300 μM, Ba2+ increased the tension of rat aortic rings concentration-dependently. Levcromakalim relaxed contractions to Ba2+ (0.5 and 1 mM) with potencies similar to those determined against KCl (25 mM) or noradrenaline as spasmogens (EC50 values 15–40 nM). The vasorelaxant effect against Ba2+ was inhibited by the KATP channel blockers, glibenclamide and tedisamil, and abolished in depolarizing medium (55 mM KCl). At 3 mM Ba2+, levcromakalim was still able to transiently induce complete relaxation; however, within 1 h oscillations in tension developed, leading to a stable level of only 15% relaxation. A similar level of relaxation was achieved against 10 mM Ba2+ whereas the combination of 0.5 mM Ba2+ and 3 μM tedisamil blocked the relaxant effect of levcromakalim completely. With minoxidil sulfate as the KATP channel opener the results of the 86Rb+ efflux and tension experiments were similar to those obtained with levcromakalim. It is concluded that Ba2+ is more potent in inhibiting the K+ channel opening than the vasorelaxant effects of the openers. On the basis of the 86Rb+ efflux experiments it is estimated that at least 97% of the channels opened by the activators can be blocked without major effects on vasorelaxation suggesting a dissociation between the two effects. However, if the block is pushed to extremes ( ≥ 99.95%) the vasorelaxant effect of the openers is also abolished suggesting a link between both effects. This paradoxon remains to be solved.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168920
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Binding of [3H]-P1075, an opener of ATP-sensitive K+ channels, to rat glomerular preparations (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 452-459 
    Details
    ISSN: 1432-1912
    Keywords: KATP channels ; Afferent arteriole ; [3H]-P1075 binding ; Glibenclamide ; U37883A ; KATP channel openers ; Sulphonylureas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract ATP-sensitive K+ channels (KATP channels) in the kidney have been found in the tubular system and in the afferent arteriole. In this study we have examined the binding of [3H]-P1075 ([3H]-N-cyano-N′-(1,1-dimethylpropyl)-N″-3-pyridylguanidine), a selective opener of KATP channels, in rat glomerular preparations. Equilibrium (saturation, competition) and kinetic experiments indicated that [3H]-P1075 binds to a single class of sites with a dissociation constant of about 3 nM and a maximum binding capacity of 10 fmol mg−1 glomerular protein. The association rate constant of the complex was 6,5×107 M−1 min−1; dissociation occurred with a half-time of 6.2 min. Specific [3H]-P1075 binding was strongly reduced when the metabolic state of the glomerular preparation was impaired during the preparation procedure or the binding assay or when the preparation was subjected to mild collagenase treatment. In different metabolically competent preparations, the amount of specific [3H]-P1075 binding correlated well with the number of vascular endings adherent to the glomeruli; no specific binding was found in mesangial cells in culture. Specific [3H]-P1075 binding was inhibited by representatives of the different classes of KATP channel openers and by sulphonylureatype blockers with inhibition constants similar to those obtained in rat aortic rings. It is concluded that rat glomerular preparations possess specific binding sites for KATP channel openers with vascular characteristics. The sensitivity of binding to mild collagenase treatment suggests that these sites are located on a membrane protein; in addition, the data suggest that these sites are localized on smooth muscle and/or renin secreting cells of the afferent vascular endings attached to some of the glomeruli. Their estimated density (1,500 μm−2) is much higher than that of KATP channels in smooth muscle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168436
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    ATP-sensitive K+ channels in the kidney (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 213-225 
    Details
    ISSN: 1432-1912
    Keywords: ATP-sensitive K+ channels (KATP channels) ; Sulphonylureas ; KATP channel openers ; Renal KATP channel blockers ; Eukalemic diuresis ; Renin secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract ATP-sensitive K+ channels (KATP channels) form a link between the metabolic state of the cell and the permeability of the cell membrane for K+ which, in turn, is a major determinant of cell membrane potential. KATP channels are found in many different cell types. Their regulation by ATP and other nucleotides and their modulation by other cellular factors such as pH and kinase activity varies widely and is fine-tuned for the function that these channels have to fulfill. In most excitable tissues they are closed and open when cell metabolism is impaired; thereby the cell is clamped in the resting state which saves ATP and helps to preserve the structural integrity of the cell. There are, however, notable exceptions from this rule; in pancreatic β-cells, certain neurons and some vascular beds, these channels are open during the normal functioning of the cell. In the renal tubular system, KATP channels are found in the proximal tubule, the thick ascending limb of Henle's loop and the cortical collecting duct. Under physiological conditions, these channels have a high open probability and play an important role in the reabsorption of electrolytes and solutes as well as in K+ homeostasis. The physiological role of their nucleotide sensitivity is not entirely clear; one consequence is the coupling of channel activity to the activity of the Na-K-ATPase (pump-leak coupling), resulting in coordinated vectorial transport. In ischemia, however, the reduced ATP/ADP ratio would increase the open probability of the KATP channels independently from pump activity; this is particularly dangerous in the proximal tubule, where 60 to 70% of the glomerular ultrafiltrate is reabsorbed. The pharmacology of KATP channels is well developed including the sulphonylureas as standard blockers and the structurally heterogeneous family of channel openers. Blockers and openers, exemplified by glibenclamide and levcromakalim, show a wide spectrum of affinities towards the different types of KATP channels. Recent cloning efforts have solved the mystery about the structure of the channel: the KATP channels in the pancreatic β-cell and in the principal cell of the renal cortical collecting duct are heteromultimers, composed of an inwardly rectifying K+ channel and sulphonylurea binding subunit(s) with unknown stoichiometry. The proteins making up the KATP channel in these two cell types are different (though homologous), explaining the physiological and pharmacological differences between these channel subtypes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171051
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Differential inhibition by tedisamil (KC 8857) and glibenclamide of the responses to cromakalim and minoxidil sulphate in rat isolated aorta (1992)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 345 (1992), S. 244-250 
    Details
    ISSN: 1432-1912
    Keywords: Tedisamil ; Glibenclamide ; Cromakalim ; Minoxidil sulphate ; Rat aorta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the K+ channel blockers tedisamil and glibenclamide on cromakalim- and minoxidil sulphate-induced 42K+ and 86Rb+ efflux and vasorelaxation in rat aorta, were investigated. In aortic strips preloaded with 42K+ or 86Rb+, cromakalim (1 μmol/l) induced increases in tracer efflux, which were concentration-dependently inhibited by tedisamil with similar potencies (pD2 ≈ 7.3) but different amplitudes (maximum inhibition of 86Rb+ efflux to 0% of control, 42K+ efflux to 10 ± 1%). The 42K+ efflux elicited by a low concentration of cromakalim (100 nmol/l) was, however, fully inhibited by tedisamil. The tracer effluxes induced by minoxidil sulphate were fully inhibited by tedisamil and glibenclamide (300 nM). Cromakalim and minoxidil sulphate, produced a concentration-dependent inhibition of noradrenaline (100 nmol/l)-induced tone, with pD2 values of ≈7.3. Tedisamil (300 nmol/1) and glibenclamide (300 nmol/l), which inhibited cromakalim- and minoxidil sulphate-induced 42K+ and 86Rb+ efflux by ≥80%, produced 2-fold and 40-fold shifts in the concentration-relaxation curve for cromakalim, and 3.5-fold and 2200-fold shifts in the concentration-relaxation curve for minoxidil sulphate, respectively. Similar shifts of the cromakalim concentration-relaxation curve in the presence of tedisamil and glibenclamide were also observed when the tissues were precontracted with potassium chloride (25 mmol/l). The results show that tedisamil and glibenclamide inhibit the cromakalim- and minoxidil sulphate-induced tracer effluxes with similar potencies whereas they differ greatly in their ability to inhibit the vasorelaxant effects of the two K+ channel openers. This suggests that the opening of 42K+/86Rb+ permeable K+ channels in the plasma membrane cannot fully explain the vasorelaxant effects of the two drugs. The mechanism(s) of vasorelaxation of cromakalim and minoxidil sulphate, which is not due to the opening of plasmalemmal K+ channels, is sensitive to inhibition by glibenclamide but comparatively insensitive to inhibition by tedisamil.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00165744
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...