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Effects of cooling on α 2 ‐adrenoceptor mediated contraction of rat tail vein
Author(s) -
Yao Mingyi,
Abel Peter W
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.933.7
Subject(s) - pertussis toxin , contraction (grammar) , phenylephrine , chemistry , medicine , guanabenz , agonist , endocrinology , biophysics , g protein , receptor , biology , biochemistry , blood pressure
a 2 ‐Adrenoceptor (a 2 ‐AR) mediated venous contraction plays an important role in thermoregulation. We investigated how cooling of rat tail vein, in vitro , affects a 2 ‐AR mediated contraction. Tail veins were isolated, endothelium removed, and incubated at 37°C or 28°C for 2.5 hrs. At 37°C the a 2 ‐AR agonist UK14304 caused contraction with an EC 50 of 11.9 nM. Cooling to 28°C decreased the EC 50 to 1.5 nM and increased maximal response by 46%. The same pattern was found with other a 2 ‐AR agonists BHT933, guanabenz and dexmedetomidine; but not with 5‐HT, angiotensin II, arginine vasopressin, and phenylephrine. The affinities (K B 's in nM) of a 2 ‐AR antagonists determined from Schild plot were increased after cooling: RX821002 (non‐selective, 2 at 37°C, 0.2 at 28°C), MK912 (a 2C ‐AR selective, 0.1 at 37°C, 0.06 at 28°C), rawolscine (a 2A/C ‐AR selective, 11 at 37°C, 1 at 28°C), ARC239 (a 2B ‐AR selective, 181 at 37°C, 68 at 28°C). K B 's for antagonists were consistent with the a 2C ‐AR subtype. UK14304 contraction was nearly eliminated by pertussis toxin at 37°C, however; pertussis toxin had little effect at 28°C. Cooling selectively increased α 2C ‐AR mediated contraction that may be due, in part, to increased affinity of α 2C ‐AR's and/or a change in α 2C ‐AR coupling to a G i protein independent pathway. Thus the development of α 2C ‐AR selective agents may be useful to modulate venous function in diseases of altered thermoregulation.