title: The surmountable effect of FSCPX, an irreversible A(1) adenosine receptor antagonist, on the negative inotropic action of A(1) adenosine receptor full agonists in isolated guinea pig left atria.
abstract: A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative inotropic effect of three A1 receptor full agonists (NECA, CPA and CHA) in isolated, paced guinea pig left atria, with the use of FSCPX, an irreversible A1 receptor antagonist. FSCPX caused an apparently pure dextral displacement of the concentration-response curves of A1 receptor agonists. Accordingly, the atrial A1 receptor function converging to inotropy showed a considerably great, approximately 80-92 % of receptor reserve for a near maximal (about 91-96 %) effect, which is greater than historical atrial A1 receptor reserve data for any effects other than inotropy. Consequently, the guinea pig atrial contractility is very sensitive to A1 receptor stimulation. Thus, it is worthwhile considering that even partial A1 receptor agonists, given in any indication, might decrease the atrial contractile force, as an undesirable side effect, in humans.
authors: Department of Pharmacology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, 4032, Hungary. gesztelyi.rudolf@pharm.unideb.hu
authors: Rudolf
authors: R
authors: Gesztelyi
authors: Zsuzsanna
authors: Z
authors: Kiss
authors: Zita
authors: Z
authors: Wachal
authors: Bela
authors: B
authors: Juhasz
authors: Mariann
authors: M
authors: Bombicz
authors: Evelin
authors: E
authors: Csepanyi
authors: Krisztian
authors: K
authors: Pak
authors: Judit
authors: J
authors: Zsuga
authors: Csaba
authors: C
authors: Papp
authors: Zoltan
authors: Z
authors: Galajda
authors: Klara
authors: K
authors: Branzaniuc
authors: Robert
authors: R
authors: Porszasz
authors: Andras Jozsef
authors: AJ
authors: Szentmiklosi
authors: Arpad
authors: A
authors: Tosaki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D058906:Purinergic P1 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D011897:Random Allocation; D043682:Receptor, Adenosine A1 / Q000502:physiology; D016896:Treatment Outcome; D014970:Xanthines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C100640:8-cyclopentyl-3-(3-((4-(fluorosulfonyl)benzoyl)oxy)propyl)-1-propylxanthine