Characterization of contractile prostanoid receptors on human airway smooth muscle.
In human bronchial rings the thromboxane A2 (TxA2) mimetic, U46619, produced cumulative concentration-related contractions up to a maximum of 141 +/- 23% of the response induced by carbachol or acetylcholine. The geometric mean EC50 value was 3.2 X 10(-8) M (95% confidence interval: 1.2, 8.9 X 10(-8) M) (n = 5). Contractions to U46619 were unaffected by atropine (10(-6) M) or verapamil (10(-5) M), but were competitively antagonized by the TxA2 antagonist GR32191 with a pA2 value of 8.40 +/- 0.41. The maximum contractile response to prostaglandin (PG) F2 alpha was smaller (90 +/- 9%, n = 13) and the potency was less (EC50 = 2 X 10(-6) M) than that of U46619. Contractions to PGF2 alpha were also competitively antagonized by GR32191 with a pA2 value of 8.18 +/- 0.08. Concentration-response curves to PGE2 were biphasic, relaxation at concentrations from 10(-9) to 10(-6) M and contraction from 10(-6) to 3 X 10(-5) M. GR32191 10(-7) M inhibited the contractile portion of the response curve in 8 of 11 tissues. Based on these results we conclude that U46619, PGF2 alpha and PGE2 all contract human airways by stimulation of the TxA2 (TP) receptor.
Armour
C L
CL
Department of Pharmacology, University of Sydney, N.S.W., Australia.
Johnson
P R
PR
Alfredson
M L
ML
Black
J L
JL
D001285:Atropine / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014700:Verapamil / Q000494:pharmacology
D001713:Biphenyl Compounds; D006538:Heptanoic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D013928:Thromboxane A2; D001285:Atropine; D002217:Carbachol; D015237:Dinoprost; D014700:Verapamil; C060013:vapiprost; D015232:Dinoprostone