Calcium and depolarization-dependent effect of pregnenolone derivatives on uterine smooth muscle.
1. The effects of several gestagens (pregnenolone [1 to 30 microM], 20 alpha-hydroxy-pregnenolone [1 to 30 microM], and 20 beta-hydroxypregnenolone [1 to 30 micro M]) on rat uterine contraction induced by KCl (60 mM) and CaCl2 (30 microM to 6 mM) have been assayed. 2. The three drugs relaxed the tonic contraction induced by KCl in a concentration-dependent way. The respective EC50 values were: 27.6 +/- 1.58 microM (pregnenolone), 4.1 +/- 0.12 microM (20 alpha-hydroxy-pregnenolone), and 11.2 +/- 1.04 microM (20 beta-hydroxypregnenolone). CaCl2 (1 to 10 mM) totally counteracted the relaxing effect of pregnenolone but only partially compared to that of 20 alpha- or 20 beta-hydroxy-pregnenolone. 3. CaCl2 (30 microM to 6 mM) produced concentration-dependent contraction of rat uterus in medium lacking calcium plus 30, 60, or 90 mM of KCl. The EC50 values of CaCl2 were: 0.38 +/- 0.072, 0.183 +/- 0.015, and 0.183 +/- 0.015 mM in a medium with 30, 60, or 90 mM of KCl, respectively. 4. Pregnenolone (10 microM) did not significantly modify the EC50 of CaCl2 in a medium with 30, 60, or 90 mM of KCl. However, 20 beta-hydroxypregnenolone (10 microM) antagonized, in a noncompetitive manner, the concentration-response curve to CaCl2. 5. 20 alpha-Hydroxypregnenolone (4 microM) antagonized the concentration-response curve to CaCl2 in a competitive manner. This antagonism was directly related to the concentration of KCl in the medium. 6. Our results suggest a different calcium antagonist effect of the three gestagens assayed.
Hidalgo
A
A
Departmento de Medicina, Facultad de Medicina, Oviedo, Spain.
Suzano
R C
RC
Revuelta
M P
MP
Sánchez-Diaz
C
C
Baamonde
A
A
Cantabrana
B
B
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002122:Calcium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
D009467:Neuromuscular Depolarizing Agents; D011189:Potassium Chloride; D011284:Pregnenolone; D002122:Calcium Chloride; D002118:Calcium