title: EP₃ receptor-mediated contraction of human pulmonary arteries and inhibition of neurogenic tachycardia in pithed rats.
abstract: BACKGROUND
  The aim of our study was (1) the pharmacological characterization of EP(3) receptors in human pulmonary arteries and (2) the examination of the potential involvement of these receptors in the regulation of neurogenic tachycardia in pithed rats. L-826266 served as the EP(3) receptor antagonist.
  
  
  METHODS
  Experiments were performed on isolated human pulmonary arteries and pithed rats.
  
  
  RESULTS
  The prostanoid EP(1)/EP(3) receptor agonist sulprostone (1 nM - 100 μM) concentration-dependently contracted isolated human pulmonary arteries (pEC50, 6.88 ± 0.10). The EP(1) receptor antagonist SC 19920 (100 μM) did not affect the vasoconstriction induced by sulprostone, the TP receptor antagonist sulotroban (10 μM) only slightly attenuated the effects elicited by sulprostone >>3 μM, whereas L-826266 (10 μM) shifted its concentration-response curve to the right (apparent pA(2) value 6.18; incubation time 0.5 h). In rings exposed to L-826266 (0.1, 1 or 10 μM) for 3 h, a concentration-dependent inhibitory effect against the sulprostone-induced vasoconstriction was obtained, yielding a Schild plot-based pA(2) value of 7.39. In pithed rats, sulprostone (10 - 1,000 nmol/kg), but not the IP/EP(1) receptor agonist iloprost (1-100 nmol/kg), inhibited the electrically evoked increase in heart rate (HR) dose-dependently, maximally by at least 80%. L-826266 (3 μmol/kg) did not affect basal HR and diastolic blood pressure, but reduced the inhibitory effect of sulprostone 1,000 nmol/kg by about 20%.
  
  
  CONCLUSIONS
  EP(3) receptors (1) located postsynaptically strongly contract human pulmonary arteries and (2) located presynaptically on sympathetic nerve fibers supplying the heart of pithed rats strongly inhibit the neurogenic tachycardia.
authors: Department of Physiology and Pathophysiology, Medical University of Bialystok, Mickiewicza 2A, PL 15-089 Białystok, Poland.
authors: Hanna
authors: H
authors: Kozłowska
authors: Marta
authors: M
authors: Baranowska-Kuczko
authors: Eberhard
authors: E
authors: Schlicker
authors: Mirosław
authors: M
authors: Kozłowski
authors: Agnieszka
authors: A
authors: Zakrzeska
authors: Emilia
authors: E
authors: Grzęda
authors: Barbara
authors: B
authors: Malinowska
mesh_terms: D000178:Acrylamides / Q000494:pharmacology; D000368:Aged; D000818:Animals; D003655:Decerebrate State; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013610:Tachycardia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000178:Acrylamides; C508710:L-826266; D009281:Naphthalenes; C545647:PTGER3 protein, human; C545649:Ptger3 protein, rat; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013449:Sulfonamides; C016767:sulprostone; C040624:sulotroban; D016285:Iloprost; D015232:Dinoprostone