Thromboxane A2 (TP) receptor in the non-pregnant porcine myometrium and its role in regulation of spontaneous contractile activity

摘要: Abstract Although there are species-related differences in uterine prostanoid receptor subtypes, functional receptors the porcine uterus similar with those human (FP, TP, EP1, EP2, EP3, DP and IP) except for TP receptor. These similarities promoted us to determine whether present non-pregnant uterus. For this purpose, effects of agonists antagonists were investigated by a contraction study binding study. 9,11-Dideoxy-9α, 11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U46619, 1 nM–10 μM), stable thromboxane A2 mimetic, caused tetrodotoxin-resistant both longitudinal circular muscles cornu. The pEC50 value muscle (6.69) was lower than that (7.62), but maximum response two times larger muscle. other regions (corpus cervix) also responded U46619, region-related difference contractile responses observed only muscles. 4(Z)-6-(2-o-Chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic (ICI192605) 7-[3-[[2-[(phenylamino)carbonyl] hydrazino]methyl]7-oxabicyclo[2.2.1]hept-2-yl]-,[1S-[1α,2α(Z),3α,4α]]-]5-heptenoic (SQ29548) inhibited U46619 competitively. cornu contained single class [3H]SQ29548 site Kd values (30 nM), Bmax (90.9±8.6 fmol/mg protein) higher (58.2±8.6 protein). ranking order competition (with pKi parentheses) [1S-[1,2(Z),3(1E,3S*),4]]-7-[3-[3-Hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic (I-BOP, 7.70)>SQ29548 (7.39)>7-[3-(3-Hydroxy-1-octenyl)bicycle[3.1.1]hept-2-yl]-,[2S-[2α(Z),3β(1E,3R*)]]-5-heptenoic (CTA2, 6.55)>7-[3-(3-hydroxy-1-octenyl)-6,6-dimethylbicyclo[3.1.1]hept-2-yl-,[1S-[1α,2β(Z),3α(1E,3R*),5α]]-5-heptenoic (PTA2, 6.50)>U46619 (6.41)>7-[5-(3-hydroxy-1-octenyl)-2-oxabicyclo[2.2.1] hept-6yl]-,[1S-[1α,4α,5α(1E,3R*),6β(Z)]]-5-heptenoic (U44069, 6.34), is consistent current receptors. Treatment indomethacin (100 nM) N-tert-butyl-N¢-[(2-cyclohexylamino-5-nitrobenzene) sulfonyl] urea (BM-531, 10 μM) spontaneous activities results indicate Therefore, subtypes exist (TP, IP, DP, FP, EP2 EP3) same as distribution differed depending on type myometrium (longitudinal muscles) region endogenous A2-TP pathway thought play physiological role regulation activity