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(The FASEB Journal. 2008;22:912.20)
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(The FASEB Journal. 2008;22:912.20.)
© 2008 FASEB

912.20

Identification of the alpha-2 adrenoceptor subtype causing contraction of rat lateral tail vein

Mingyi Yao and Peter W Abel

Pharmacology, Creighton University, Omaha, NE

ABSTRACT

Constriction of veins plays an important role in thermoregulation. Norepinephrine from sympathetic nerves can activate alpha-2 adrenoceptors in veins causing constriction and reduced heat loss in response to cooling. We determined the alpha-2 adrenoceptor subtype causing contraction of the rat lateral tail vein studied in vitro. Tail veins were isolated, endothelium removed, and incubated in Krebs solution at 37 degrees C. Concentration-response curves for contraction caused by the alpha-2 adrenoceptor agonist UK 14304 were generated in the absence and presence of the alpha-2 adrenoceptor antagonists RX 821002 (non-subtype selective), BRL 44408 (alpha-2A selective), ARC 239 (alpha-2B/C selective) and MK 912 (alpha-2C selective). UK 14304 caused concentration-dependent contraction of the tail vein with an EC50 of 8.3 nM. The affinities (KB) of antagonists in blocking UK14304 contraction were RX 821002 (2.3 nM), BRL 44408 (64 nM), ARC 239 (199 nM) and MK 912 (0.06 nM). The affinity of MK 912 was nearly the same as its affinity for alpha-2C adrenoceptors reported by others, and affinities for other antagonists were consistent with alpha-2C adrenoceptors. Thus, alpha-2C adrenoceptors mediate UK 14304 induced contraction of the rat lateral tail vein. The development of alpha-2C selective agents may be useful to selectively regulate venous function in diseases associated with altered thermoregulation.





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