The effects of 2-aminoethoxydiphenyl borate, a novel inositol 1,4, 5-trisphosphate receptor modulator on myometrial contractions.
These studies were performed to evaluate the effect of 2-aminoethoxydiphenyl borate (2-APB), a novel membrane-permeable inositol 1,4,5-trisphosphate-receptor inhibitor on agonist-induced, spontaneous, and KCl-stimulated in vitro myometrial contractions. 2-APB significantly inhibited spontaneous myometrial contractions as well as phasic contractions induced by various uterotonic agonists. Confiriming its effects on intracellular calcium release, 2-APB inhibited phasic contractions in the absence of extracellular calcium. 2-APB had little effect on the tonic response to KCl stimulation, implicating its insignificant effect on voltage-gated calcium channels. The inhibitory effect of 2-APB on phasic contractions was completely reversed by washout. In summary, 2-APB effectively penetrated uterine tissue and significantly inhibited myometrial events previously shown to be mediated through activation of the PI-signaling pathway.
Ascher-Landsberg
J
J
Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois, 60637, USA.
Saunders
T
T
Elovitz
M
M
Phillippe
M
M
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D005260:Female; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009215:Myometrium / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*
D001896:Boron Compounds; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C109986:2-aminoethoxydiphenyl borate