Role of nucleotide cyclases in the inhibition of pregnant rat uterine contractions by the openers of potassium channels.
OBJECTIVE
Our objective was to study the involvement of adenylate and guanylate cylases in spontaneous uterine contractions and inhibition induced by the opening of potassium channels.


METHODS
Uterine rings from rats at mid and term gestation and from rats at term gestation in labor were suspended in organ chambers for isometric tension recording. Concentration-response relationships to an opener of adenosine triphosphate-dependent potassium channels, levcromakalim, or to an opener of calcium-dependent potassium channels, NS 1619, were studied in the absence and presence of inhibitors of adenylate cyclase (MDL 12330 A, 2 x 10(-5) mol/L; SQ 22536, 10(-4) mol/L) or guanylate cyclase (LY 83583,3 x 10(-6) mol/L).


RESULTS
MDL 12330 A and SQ 22536 accentuated contractions in rings from rats at mid gestation but not at term gestation or at term gestation in labor. LY 83583 inhibited contractions in the rings from all 3 groups. Levcromakalim was equally effective in inhibiting contractions of rings from all 3 groups. MDL 12330 A, but not SQ 22536, decreased sensitivity and maximal inhibition induced by levcromakalim (term gestation greater than mid gestation greater than term gestation in labor). LY 83583 decreased the sensitivity to and maximal inhibition induced by levcromakalim in rings from pregnant rats at mid gestation. NS 1619 attenuated contraction of rings from rats at mid gestation and, to a lesser extent, at term gestation but accentuated contractions in rings from animals at term gestation in labor. MDL 12330 A, but not SQ 22536 or LY 83583, attenuated the changes induced by NS 1619 in rings from all 3 groups.


CONCLUSIONS
(1) The influence of nucleotide cyclases on basal uterine contractility depends on gestational age. (2) The inhibition of uterine contractions that results from the opening of calcium-dependent potassium channels depends on adenylate cyclase, whereas that of adenosine triphosphate-dependent potassium channels depends on both adenylate and guanylate cyclases. 3. Activation of adenosine triphosphate-dependent potassium channels is more efficient than activation of calcium-dependent potassium channels. 4. The inhibition induced by calcium-dependent potassium channel openers, but not adenosine triphosphate-dependent potassium channel openers, decreases as pregnancy progresses, and at delivery the activation of spontaneous contractile activity is evident.
Okawa
T
T
Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, 77555-1062, USA.
Longo
M
M
Vedernikov
Y P
YP
Chwalisz
K
K
Saade
G R
GR
Garfield
R E
RE
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000502:physiology*; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*
D000067956:Adenylyl Cyclase Inhibitors; D000634:Aminoquinolines; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D019806:Cromakalim; C086491:NS 1619; C017759:9-(tetrahydro-2-furyl)-adenine; C041715:6-anilino-5,8-quinolinedione; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000225:Adenine