The effect of extracellular adenosine triphosphate on the spontaneous contractility of human myometrial strips.
OBJECTIVE
Extracellular ATP is involved in cell-cell signalling in a variety of tissues but its effects in tissue level signalling in the myometrium have been poorly studied to date. We hypothesised that extracellular ATP was involved in the control of myometrial contractile frequency and/or force.


METHODS
In vitro study of the effect of altering the concentration of extracellular ATP on the spontaneous contractility of human myometrial strips obtained from term elective caesarean sections.


RESULTS
Decreasing extracellular ATP levels by the ectoATP-ase agent apyrase VI (1-50 units/mL) produced a dose dependent decrease in contractile frequency (decrease of 46.3% compared with the baseline frequency at 20 units/mL, p=0.001, n=6). Contractility was unchanged by apyrase VII (20 units/mL), an agent with relatively greater ADPase activity, indicating an effect via ATP and not ADP. Contractile frequency increased after addition of ATP 10-100 microM (an increase to 145.8% of baseline frequency at 100 microM: 126.1-165.5%, p=0.005, n=7) or the ATPase inhibitor ARL at 100 microM (an increase to 136.3% of the baseline frequency: 107.1-165.5, p=0.03, n=7). Contractile force remained unchanged by these agents.


CONCLUSIONS
Extracellular ATP shows a dose-response relationship to contractile frequency but does not affect contractile force. Consequently it may be involved in the pacemaking mechanism for the generation of uterine contractions.
Hutchings
Graham
G
Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium. graham.hutchings@uclouvain.be
Gevaert
Thomas
T
Deprest
Jan
J
Nilius
Bernd
B
Williams
Olivia
O
De Ridder
Dirk
D
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001081:Apyrase / Q000494:pharmacology; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009215:Myometrium / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
D000255:Adenosine Triphosphate; D001081:Apyrase