Adenylate cyclase and potassium channels are involved in forskolin- and 1,9-dideoxyforskolin-induced inhibition of pregnant rat uterus contractility

Yuri P. Vedernikov, Ashu S. Syal, Toshiaki Okawa, George Saade, Robert E. Garfield

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

OBJECTIVE: We sought to study the contribution of potassium channels in the effect of forskolin and 1,9-dideoxyforskolin on uterine contractility in the pregnant rat. STUDY DESIGN: Rings taken from the middle portions of uterine horns from rats at 16 days of gestation were positioned in organ chambers containing physiologic salt solution bubbled with 5% carbon dioxide in air (37°C, pH ~7.4) for isometric tension recording under 2 g passive tension. The effects of cumulative concentrations of forskolin and 1,9- dideoxyforskolin in the absence or presence of an adenylate cyclase inhibitor (MDL-12,330A, 10-5 mol/L), a nonselective potassium channel blocker (tetrabutylammonium, 10-4 mol/L), or an adenosine triphosphate-dependent potassium channel blocker (glibendamide 10-5 mol/L) were studied. RESULTS: Both forskolin and, to a lesser extent, 1,9-dideoxyforskolin inhibit uterine contractions. Tetrabutylammonium, glibenclamide, and MDL-12,330A attenuated the effects of forskolin, whereas glibenclamide was less effective against 1,9-dideoxyforskolin. CONCLUSION: Activation of adenylate cyclases, as well as adenosine triphosphate-dependent potassium channels and, to a greater extent, calcium-dependent potassium channels, is involved in the inhibitory effect of forskolin in uterine rings from rats at 16 days of gestation. Inhibition of uterine contractions by 1,9-dideoxyforskolin is less than that by forskolin and involves activation of adenylate cyclase and calcium- dependent potassium channels. Whether activation of guanylate cyclase is involved in the effect of the agents on calcium-dependent potassium channels needs further investigation. 1,9-Dideoxyforskolin is not an inactive isomer of forskolin in rat uterine rings.

Original languageEnglish (US)
Pages (from-to)620-624
Number of pages5
JournalAmerican Journal of Obstetrics and Gynecology
Volume182
Issue number3
StatePublished - 2000

Fingerprint

Potassium Channels
Colforsin
Adenylyl Cyclases
Uterus
Calcium-Activated Potassium Channels
Potassium Channel Blockers
Uterine Contraction
Glyburide
Adenosine Triphosphate
Pregnancy
Guanylate Cyclase
1,9-dideoxyforskolin
Carbon Dioxide
Salts
Air

Keywords

  • 1,9-dideoxyforskolin
  • Adenylate cyclases
  • Forskolin
  • Glibenclamide
  • MDL-12,330A
  • Potassium channels
  • Tetrabutylammonium chloride

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Adenylate cyclase and potassium channels are involved in forskolin- and 1,9-dideoxyforskolin-induced inhibition of pregnant rat uterus contractility. / Vedernikov, Yuri P.; Syal, Ashu S.; Okawa, Toshiaki; Saade, George; Garfield, Robert E.

In: American Journal of Obstetrics and Gynecology, Vol. 182, No. 3, 2000, p. 620-624.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE: We sought to study the contribution of potassium channels in the effect of forskolin and 1,9-dideoxyforskolin on uterine contractility in the pregnant rat. STUDY DESIGN: Rings taken from the middle portions of uterine horns from rats at 16 days of gestation were positioned in organ chambers containing physiologic salt solution bubbled with 5{\%} carbon dioxide in air (37°C, pH ~7.4) for isometric tension recording under 2 g passive tension. The effects of cumulative concentrations of forskolin and 1,9- dideoxyforskolin in the absence or presence of an adenylate cyclase inhibitor (MDL-12,330A, 10-5 mol/L), a nonselective potassium channel blocker (tetrabutylammonium, 10-4 mol/L), or an adenosine triphosphate-dependent potassium channel blocker (glibendamide 10-5 mol/L) were studied. RESULTS: Both forskolin and, to a lesser extent, 1,9-dideoxyforskolin inhibit uterine contractions. Tetrabutylammonium, glibenclamide, and MDL-12,330A attenuated the effects of forskolin, whereas glibenclamide was less effective against 1,9-dideoxyforskolin. CONCLUSION: Activation of adenylate cyclases, as well as adenosine triphosphate-dependent potassium channels and, to a greater extent, calcium-dependent potassium channels, is involved in the inhibitory effect of forskolin in uterine rings from rats at 16 days of gestation. Inhibition of uterine contractions by 1,9-dideoxyforskolin is less than that by forskolin and involves activation of adenylate cyclase and calcium- dependent potassium channels. Whether activation of guanylate cyclase is involved in the effect of the agents on calcium-dependent potassium channels needs further investigation. 1,9-Dideoxyforskolin is not an inactive isomer of forskolin in rat uterine rings.",
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T1 - Adenylate cyclase and potassium channels are involved in forskolin- and 1,9-dideoxyforskolin-induced inhibition of pregnant rat uterus contractility

AU - Vedernikov, Yuri P.

AU - Syal, Ashu S.

AU - Okawa, Toshiaki

AU - Saade, George

AU - Garfield, Robert E.

PY - 2000

Y1 - 2000

N2 - OBJECTIVE: We sought to study the contribution of potassium channels in the effect of forskolin and 1,9-dideoxyforskolin on uterine contractility in the pregnant rat. STUDY DESIGN: Rings taken from the middle portions of uterine horns from rats at 16 days of gestation were positioned in organ chambers containing physiologic salt solution bubbled with 5% carbon dioxide in air (37°C, pH ~7.4) for isometric tension recording under 2 g passive tension. The effects of cumulative concentrations of forskolin and 1,9- dideoxyforskolin in the absence or presence of an adenylate cyclase inhibitor (MDL-12,330A, 10-5 mol/L), a nonselective potassium channel blocker (tetrabutylammonium, 10-4 mol/L), or an adenosine triphosphate-dependent potassium channel blocker (glibendamide 10-5 mol/L) were studied. RESULTS: Both forskolin and, to a lesser extent, 1,9-dideoxyforskolin inhibit uterine contractions. Tetrabutylammonium, glibenclamide, and MDL-12,330A attenuated the effects of forskolin, whereas glibenclamide was less effective against 1,9-dideoxyforskolin. CONCLUSION: Activation of adenylate cyclases, as well as adenosine triphosphate-dependent potassium channels and, to a greater extent, calcium-dependent potassium channels, is involved in the inhibitory effect of forskolin in uterine rings from rats at 16 days of gestation. Inhibition of uterine contractions by 1,9-dideoxyforskolin is less than that by forskolin and involves activation of adenylate cyclase and calcium- dependent potassium channels. Whether activation of guanylate cyclase is involved in the effect of the agents on calcium-dependent potassium channels needs further investigation. 1,9-Dideoxyforskolin is not an inactive isomer of forskolin in rat uterine rings.

AB - OBJECTIVE: We sought to study the contribution of potassium channels in the effect of forskolin and 1,9-dideoxyforskolin on uterine contractility in the pregnant rat. STUDY DESIGN: Rings taken from the middle portions of uterine horns from rats at 16 days of gestation were positioned in organ chambers containing physiologic salt solution bubbled with 5% carbon dioxide in air (37°C, pH ~7.4) for isometric tension recording under 2 g passive tension. The effects of cumulative concentrations of forskolin and 1,9- dideoxyforskolin in the absence or presence of an adenylate cyclase inhibitor (MDL-12,330A, 10-5 mol/L), a nonselective potassium channel blocker (tetrabutylammonium, 10-4 mol/L), or an adenosine triphosphate-dependent potassium channel blocker (glibendamide 10-5 mol/L) were studied. RESULTS: Both forskolin and, to a lesser extent, 1,9-dideoxyforskolin inhibit uterine contractions. Tetrabutylammonium, glibenclamide, and MDL-12,330A attenuated the effects of forskolin, whereas glibenclamide was less effective against 1,9-dideoxyforskolin. CONCLUSION: Activation of adenylate cyclases, as well as adenosine triphosphate-dependent potassium channels and, to a greater extent, calcium-dependent potassium channels, is involved in the inhibitory effect of forskolin in uterine rings from rats at 16 days of gestation. Inhibition of uterine contractions by 1,9-dideoxyforskolin is less than that by forskolin and involves activation of adenylate cyclase and calcium- dependent potassium channels. Whether activation of guanylate cyclase is involved in the effect of the agents on calcium-dependent potassium channels needs further investigation. 1,9-Dideoxyforskolin is not an inactive isomer of forskolin in rat uterine rings.

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KW - Forskolin

KW - Glibenclamide

KW - MDL-12,330A

KW - Potassium channels

KW - Tetrabutylammonium chloride

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EP - 624

JO - American Journal of Obstetrics and Gynecology

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