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Inhibitory effects of the ATP-sensitive potassium channel openers cromakalim, pinacidil and minoxidil on the carbachol-response curve in porcine detrusor muscle.

Badawi JK, Kirschner-Hermanns R, Ding A - Arab J Urol (2012)

Bottom Line: Cromakalim had the greatest inhibitory effect, significantly suppressing the carbachol-response curve at 10(-6) and 10(-5) M.Pinacidil showed a significant inhibitory effect at 10(-5.5) and 10(-5) M, which was smaller than that of cromakalim.Minoxidil did not significantly inhibit the contractions at all examined concentrations.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University Hospital of Mannheim, Medical Faculty of the Ruprecht Karls-University Heidelberg, Germany.

ABSTRACT

Aims: ATP-sensitive potassium channels represent promising drug targets for treating specific bladder diseases. The inhibitory effects of ATP-selective potassium channel openers (PCOs) on the carbachol-response curve in porcine detrusor muscle were examined.

Materials and methods: Each of the three substances used in the study represent one prototype of a different class of PCO: cromakalim belongs to the benzopyran series, pinacidil is a cyanoguanidine derivative, and minoxidil represents a pyrimidine derivative. The porcine detrusor muscle represents one of the best models for human detrusor. Experiments were conducted on muscle strips of porcine detrusor muscle suspended in a tissue bath. Concentration-response curves of carbachol were constructed after pretreatment with cromakalim at 10(-7), 10(-6) and 10(-5) M, and with pinacidil and minoxidil at 10(-6), 10(-5.5) and 10(-5) M, respectively. Each muscle strip was only used to examine one concentration of one substance.

Results: Cromakalim had the greatest inhibitory effect, significantly suppressing the carbachol-response curve at 10(-6) and 10(-5) M. Pinacidil showed a significant inhibitory effect at 10(-5.5) and 10(-5) M, which was smaller than that of cromakalim. Minoxidil did not significantly inhibit the contractions at all examined concentrations.

Conclusions: The examined ATP-sensitive PCOs belonging to the benzopyrans and cyanoguanidines significantly suppressed detrusor contractions. The development of derivatives of these prototypes could open new possibilities for the pharmacological treatment of selected bladder diseases.

No MeSH data available.


Related in: MedlinePlus

The mean cumulative CRCs of carbachol after pretreatment with pinacidil at 10−6 M (A: n, N = 8, control group n = 10, N = 9), 10−5.5 M (B: n, N = 5, control group n, N = 5–6) and 10−5 M (C: n = 5–6, N = 5, control group: n = 7–8, N = 6–7). Details as Fig. 1.
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f0010: The mean cumulative CRCs of carbachol after pretreatment with pinacidil at 10−6 M (A: n, N = 8, control group n = 10, N = 9), 10−5.5 M (B: n, N = 5, control group n, N = 5–6) and 10−5 M (C: n = 5–6, N = 5, control group: n = 7–8, N = 6–7). Details as Fig. 1.

Mentions: The CRCs for carbachol are shown in Fig. 2 after pretreatment with pinacidil at 10−6 M (A), 10−5.5 M (B) and 10−5 M (C). The CRC was significantly suppressed at 10−5.5 and 10−5 M. The maximum carbachol-induced contraction after pretreatment with pinacidil in the different concentrations and the corresponding value of each control group in which only the solvent was present is shown in Table 1. The unpaired two-tailed Student’s t-test showed no significant difference in the maximum carbachol-induced contraction.


Inhibitory effects of the ATP-sensitive potassium channel openers cromakalim, pinacidil and minoxidil on the carbachol-response curve in porcine detrusor muscle.

Badawi JK, Kirschner-Hermanns R, Ding A - Arab J Urol (2012)

The mean cumulative CRCs of carbachol after pretreatment with pinacidil at 10−6 M (A: n, N = 8, control group n = 10, N = 9), 10−5.5 M (B: n, N = 5, control group n, N = 5–6) and 10−5 M (C: n = 5–6, N = 5, control group: n = 7–8, N = 6–7). Details as Fig. 1.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4442889&req=5

f0010: The mean cumulative CRCs of carbachol after pretreatment with pinacidil at 10−6 M (A: n, N = 8, control group n = 10, N = 9), 10−5.5 M (B: n, N = 5, control group n, N = 5–6) and 10−5 M (C: n = 5–6, N = 5, control group: n = 7–8, N = 6–7). Details as Fig. 1.
Mentions: The CRCs for carbachol are shown in Fig. 2 after pretreatment with pinacidil at 10−6 M (A), 10−5.5 M (B) and 10−5 M (C). The CRC was significantly suppressed at 10−5.5 and 10−5 M. The maximum carbachol-induced contraction after pretreatment with pinacidil in the different concentrations and the corresponding value of each control group in which only the solvent was present is shown in Table 1. The unpaired two-tailed Student’s t-test showed no significant difference in the maximum carbachol-induced contraction.

Bottom Line: Cromakalim had the greatest inhibitory effect, significantly suppressing the carbachol-response curve at 10(-6) and 10(-5) M.Pinacidil showed a significant inhibitory effect at 10(-5.5) and 10(-5) M, which was smaller than that of cromakalim.Minoxidil did not significantly inhibit the contractions at all examined concentrations.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University Hospital of Mannheim, Medical Faculty of the Ruprecht Karls-University Heidelberg, Germany.

ABSTRACT

Aims: ATP-sensitive potassium channels represent promising drug targets for treating specific bladder diseases. The inhibitory effects of ATP-selective potassium channel openers (PCOs) on the carbachol-response curve in porcine detrusor muscle were examined.

Materials and methods: Each of the three substances used in the study represent one prototype of a different class of PCO: cromakalim belongs to the benzopyran series, pinacidil is a cyanoguanidine derivative, and minoxidil represents a pyrimidine derivative. The porcine detrusor muscle represents one of the best models for human detrusor. Experiments were conducted on muscle strips of porcine detrusor muscle suspended in a tissue bath. Concentration-response curves of carbachol were constructed after pretreatment with cromakalim at 10(-7), 10(-6) and 10(-5) M, and with pinacidil and minoxidil at 10(-6), 10(-5.5) and 10(-5) M, respectively. Each muscle strip was only used to examine one concentration of one substance.

Results: Cromakalim had the greatest inhibitory effect, significantly suppressing the carbachol-response curve at 10(-6) and 10(-5) M. Pinacidil showed a significant inhibitory effect at 10(-5.5) and 10(-5) M, which was smaller than that of cromakalim. Minoxidil did not significantly inhibit the contractions at all examined concentrations.

Conclusions: The examined ATP-sensitive PCOs belonging to the benzopyrans and cyanoguanidines significantly suppressed detrusor contractions. The development of derivatives of these prototypes could open new possibilities for the pharmacological treatment of selected bladder diseases.

No MeSH data available.


Related in: MedlinePlus