title: Pharmacological characterization of FE 201874, the first selective high affinity rat V1A vasopressin receptor agonist.
abstract: OBJECTIVE
  Distinct vasopressin receptors are involved in different physiological and behavioural functions. Presently, no selective agonist is available to specifically elucidate the functional roles of the V1A receptor in the rat, one of the most widely used animal models. FE 201874 is a new derivative of the human selective V1A receptor agonist F180. In this study, we performed a multi-approach pharmacological and functional characterization of FE 201874 to determine whether it is selective for V1A receptors.
  
  
  METHODS
  We modified an available human selective V1A receptor agonist (F180) and determined its pharmacological properties in cell lines expressing vasopressin/oxytocin receptors (affinity and coupling to second messenger cascades), in an ex vivo model (aorta ring contraction) and in vivo in rats (proliferation of adrenal cortex glomerulosa cells and lactation).
  
  
  RESULTS
  FE 201874 exhibited nanomolar affinity for the rat V1A receptor; it was highly selective towards the rat V1B and V2 vasopressin receptors and behaved as a full V1A agonist in all the pharmacological tests performed. FE 201874 bound to the oxytocin receptor, but with moderate affinity, and behaved as an oxytocin antagonist in vitro, but not in vivo.
  
  
  CONCLUSIONS
  On functional grounds, all the data demonstrate that FE 201874 is the first selective agonist of the rat V1A receptor isoform available. Hence, FE 201874 may have potential as a treatment for the vasodilator-induced hypotension occurring in conditions such as septic shock and could be the most suitable compound for discriminating between the behavioural effects of arginine vasopressin and oxytocin.
authors.affiliation: CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, F-34094, France; INSERM, U661, Montpellier, F-34094, France; Universités de Montpellier 1 & 2, UMR-5203, Montpellier, F-34094, France; Université Constantine 1, Faculté des sciences de la nature et de la vie, Constantine, Algérie.
authors.forename: Rafik
authors.initials: R
authors.lastname: Marir
authors.forename: Anne
authors.initials: A
authors.lastname: Virsolvy
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Wisniewski
authors.forename: Julie
authors.initials: J
authors.lastname: Mion
authors.forename: Dominique
authors.initials: D
authors.lastname: Haddou
authors.forename: Evelyne
authors.initials: E
authors.lastname: Galibert
authors.forename: Zahia
authors.initials: Z
authors.lastname: Meraihi
authors.forename: Michel G
authors.initials: MG
authors.lastname: Desarménien
authors.forename: Gilles
authors.initials: G
authors.lastname: Guillon
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007774:Lactation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000819:agonists* / Q000378:metabolism; D013045:Species Specificity; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects
chemical_list: C000591332:FE 201874; D010456:Peptides, Cyclic; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; C582098:V1a vasopressin receptor, rat
keywords: FE 201874; V1A receptor; Vasopressin agonist; aorta contraction; glomerulosa cell proliferation