Pharmacological nature of TP receptor mediated contraction in human intrapulmonary artery

Abstract The present experiments were undertaken to elucidate the pharmacological nature of thromboxane A 2 /prostaglandin H 2 receptor (TP)-mediated contraction in human intrapulmonary arteries. 9,11-epithio-11, 12-methano-thromboxane A 2 (STA 2 ) and (15S)-hydroxy-9α, 11α-(epoxymethano) prosta-5Z, 13E-dienoic acid (U46619) (TXA 2 agonists) caused contractions in a concentration-dependent manner with EC 50 values of 1.4 × 10 −9 M and 3.1 × 10 −9 M, respectively. S-1452 and ONO-3708 (TP receptor antagonists) concentration-dependently attenuated the STA 2 (10−8 M)-induced contraction with IC 50 values of 5.8 × 10 −9 M and 4.2 × 10 −8 M, respectively. U-73122 (3 × 10 −6 M) and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (3 × 10 −5 M) (phospholipase C inhibitors) significantly attenuated the STA 2 -induced contraction. Ca ++ -induced contraction in the presence of STA 2 (10 −8 M) in Ca ++ -free medium was attenuated by nifedipine (10 −6 M) by 40 %. The remaining nifedipine-resistant Ca ++ -induced contraction was not attenuated by nitroglycerin (10 −5 M), but forskolin (10 −5 M) (adenylate cyclase stimulant) significantly decreased it by 75 %. The results clearly indicate that in human intrapulmonary artery, there are TP receptors coupled with phospholipase C activation and that TP receptor-mediated Ca ++ -mobilization is in part nifedipine- and nitroglycerin-resistant, but forskolin-sensitive.