The bronchodilators 8-iso-prostaglandin E2 and prostaglandin E2 induce K+ current suppression via thromboxane A2 receptors in porcine tracheal smooth muscle.
We examined relaxations and changes in K(+) current evoked by 8-iso-prostaglandin E(2) and prostaglandin E(2) in porcine tracheal smooth muscle. Both autacoids completely reversed cholinergic tone; blockade of thromboxane A(2) receptors had no effect on relaxations to either compound. 8-iso-prostaglandin E(2) and prostaglandin E(2) suppressed outward K(+) currents while the thromboxane A(2) receptor agonist U46619 (9, 11-dideoxy-9a,11a-methanoepoxy prostaglandin F(2alpha)) had no significant effect. During thromboxane A(2) receptor antagonism, however, 8-iso-prostaglandin E(2) markedly augmented K(+) currents while prostaglandin E(2) no longer suppressed K(+) currents, indicating that the inhibition of K(+) currents by both compounds was thromboxane A(2) receptor-mediated. Furthermore, the observation that K(+) currents were augmented by 8-iso-prostaglandin E(2) but not by prostaglandin E(2) suggests that the salutory effect is not exerted through a prostaglandin E receptor. Additionally, our observations argue against any causal role for K(+) current activation in mediating relaxations evoked by isoprostanes or by prostaglandin E(2). We conclude that 8-iso-prostaglandin E(2) relaxes porcine tracheal smooth muscle independent of K(+) current activity, and that 8-iso-prostaglandin E(2) may also act at a non-thromboxane A(2)/non-prostaglandin E receptor to augment K(+) currents.
Asthma Research Group, Father Sean O'Sullivan Research Centre, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Peter B
PB
Helli
Adriana
A
Catalli
Luke J
LJ
Janssen
D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D028421:Isoprostanes / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000502:physiology*; D013552:Swine; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001993:Bronchodilator Agents; D028421:Isoprostanes; D015221:Potassium Channels; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D015232:Dinoprostone; C011987:8-isoprostaglandin E2