Pharmacological nature of TP receptor mediated contraction in human intrapulmonary artery.
The present experiments were undertaken to elucidate the pharmacological nature of thromboxane A2/prostaglandin H2 receptor (TP)-mediated contraction in human intrapulmonary arteries. 9,11-epithio-11, 12-methano-thromboxane A2 (STA2) and (15S)-hydroxy-9 alpha, 11 alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid (U46619) (TXA2 agonists) caused contractions in a concentration-dependent manner with EC50 values of 1.4 x 10(-9) M and 3.1 x 10(-9) M, respectively. S-1452 and ONO-3708 (TP receptor antagonists) concentration-dependently attenuated the STA2 (10(-8) M)-induced contraction with IC50 values of 5.8 x 10(-9) M and 4.2 x 10(-8) M, respectively. U-73122 (3 x 10(-6) M) and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (3 x 10(-5) M) (phospholipase C inhibitors) significantly attenuated the STA2-induced contraction. Ca(+2)-induced contraction in the presence of STA2 (10(-8) M) in Ca(+2)-free medium was attenuated by nifedipine (10(-6) M) by 40%. The remaining nifedipine-resistant Ca(+2)-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(+2)-mobilization is in part nifedipine- and nitroglycerin-resistant, but forskolin-sensitive.
Jino
H
H
Pharmacology Division, Radioisotope Research Center, Kyoto University, Japan.
Kurahashi
K
K
Usui
H
H
Nakata
Y
Y
Shimizu
Y
Y
Temma
S
S
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000502:physiology; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2 / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D011982:Receptors, Prostaglandin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D005576:Colforsin; D013928:Thromboxane A2; D010738:Type C Phospholipases; D005996:Nitroglycerin; D009543:Nifedipine; D002118:Calcium