TY - JOUR
T1 - Characterization of tolerance to the anti-leakage effect of formoterol in rat airways
AU - Bowden, Jeffrey J.
AU - Anderson, Gary P.
AU - Lefevre, Peter M.
AU - Sulakvelidze, Irakly
AU - McDonald, Donald M.
PY - 1997/10/29
Y1 - 1997/10/29
N2 - These experiments addressed the question of whether the anti-plasma leakage action of β2-adrenoceptor agonists in rat airways is subject to tolerance. Pathogen-free F344 rats were pretreated with the highly selective, long-acting β2-adrenoceptor agonist, formoterol (0, 0.1, 1, 10 μg/kg, i.p.) for 7 days; 24 h later the effectiveness of acute doses of formoterol (0, 0.1, 1, 10 μg/kg, i.v.) was tested against substance P-induced plasma leakage. The anti-leakage effect of formoterol was not subject to tolerance with the low or intermediate pretreatment dose. Pretreatment with 10 μg/kg formoterol reduced the effectiveness of the 1 μg/kg acute dose but not the 10 I.μg/kg acute dose. We conclude that tolerance to the anti-leakage effect of formoterol can occur, but airway vessels are likely to retain functionally coupled receptors even after high dose pretreatment.
AB - These experiments addressed the question of whether the anti-plasma leakage action of β2-adrenoceptor agonists in rat airways is subject to tolerance. Pathogen-free F344 rats were pretreated with the highly selective, long-acting β2-adrenoceptor agonist, formoterol (0, 0.1, 1, 10 μg/kg, i.p.) for 7 days; 24 h later the effectiveness of acute doses of formoterol (0, 0.1, 1, 10 μg/kg, i.v.) was tested against substance P-induced plasma leakage. The anti-leakage effect of formoterol was not subject to tolerance with the low or intermediate pretreatment dose. Pretreatment with 10 μg/kg formoterol reduced the effectiveness of the 1 μg/kg acute dose but not the 10 I.μg/kg acute dose. We conclude that tolerance to the anti-leakage effect of formoterol can occur, but airway vessels are likely to retain functionally coupled receptors even after high dose pretreatment.
KW - β-Adrenergic agonist
KW - Plasma leakage
KW - Substance P
KW - Trachea
KW - Vascular permeability
UR - http://www.scopus.com/inward/record.url?scp=0030669620&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(97)01272-7
DO - 10.1016/S0014-2999(97)01272-7
M3 - Article
C2 - 9408007
AN - SCOPUS:0030669620
SN - 0014-2999
VL - 338
SP - 83
EP - 87
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -