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Redefining Agonist Selectivity at Vascular α1‐ and α2‐Adrenoceptors
Author(s) -
Crassous PierreAntoine,
Flavahan Sheila,
Flavahan Nicholas
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.933.4
Subject(s) - rauwolscine , prazosin , phenylephrine , agonist , chemistry , antagonist , norepinephrine , medicine , constriction , vasoconstriction , endocrinology , pharmacology , receptor , biochemistry , blood pressure , dopamine
Phenylephrine is considered a selective α1‐adrenoceptor (α1‐AR) agonist and is widely used to characterize these receptors. We observed that the selective α2‐AR antagonist rauwolscine reversed phenylephrine‐induced constriction in isolated mice tail arteries. Experiments were therefore performed to assess the selectivity of phenylephrine and other α‐AR agonists in this blood vessel. Concentration‐effect curves to the α‐AR agonists phenylephrine, cirazoline or norepinephrine were not affected by rauwolscine (3x10‐8M). The selective α1‐AR antagonist prazosin (10‐7M) caused non‐parallel shifts in concentration‐effect curves to these agonists being more potent at high compared to low levels of constriction. After prazosin, rauwolscine (3x10‐8M) inhibited concentration‐effect curves more at low compared to high levels of constriction. Indeed, the combination of prazosin plus rauwolscine caused parallel shifts in the concentration‐effect curves to these agonists. The α2‐AR agonist UK14304 caused a low‐maximum constriction compared to the other α‐AR agonists. Responses to UK 14,304 were inhibited by rauwolscine (3x10‐8M) but not by prazosin (10‐7M). Therefore, phenylephrine, cirazoline or norepinephrine constrict mouse tail arteries by activating α1 and α2‐ARs. Based on antagonist potency, the order of selectivity for α1‐ARs is cirazoline > phenylephrine = norepinephrine.