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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries.

PURPOSE: An investigation into whether alpha(2)-adrenoceptor agonists induce contractions in the porcine ciliary arteries and to characterize the functional receptor subtype mediating these responses. METHODS: Isolated arteries from the intraocular part of the porcine ciliary artery were suspended in microvascular myographs for isometric tension recording. The segments were contracted with the alpha(2)-adrenoceptor agonists brimonidine, apraclonidine, and oxymetazoline. To determine which subtypes of the alpha(2)-adrenoceptor mediate this contraction, antagonists subselective for the different alpha(2)-adrenoceptors were added to the vessel bath before concentration-response curves for brimonidine were obtained. The following alpha(2)-adrenoceptor antagonists were applied: BRL44408 (alpha(2A)-selective), ARC239 (alpha(2B)- and alpha(2C)-selective), and prazosin (alpha(2B)- and alpha(2C)-selective). RESULTS: The alpha(2)-adrenoceptor agonists induced vasoconstriction in the porcine ciliary artery with the following potency order (EC(50)) expressed in nanomolar: brimonidine 2.11, oxymetazoline 5.26, and apraclonidine 13. 0. As a reference, noradrenaline was tested, and its EC(50) was determined to be 247 nM in the ciliary artery. In the porcine ciliary arteries BRL44408, ARC239, and prazosin caused concentration-dependent and parallel rightward shifts of the concentration-response curves for brimonidine. Schild analyses for the antagonists against brimonidine yielded regression lines with slopes of unity and functional antagonist potencies (pK(B)) for BRL44408 (7.8), ARC 239 (5.8) and for prazosin (6.0) suggesting the presence of functional alpha(2A)-adrenoceptors. Moreover, there was a good correlation of pK(B) with ligand-binding affinity (pK(i)) of the alpha(2A)-adrenoceptor in the porcine eye tissue. CONCLUSIONS: The alpha(2)-adrenoceptor agonists brimonidine, apraclonidine, and oxymetazoline are potent vasoconstrictors in the porcine ciliary artery. In the present work, it was shown for the first time that the alpha(2A)-adrenoceptor subtype mediates this contraction.[1]


  1. Potent alpha(2A)-adrenoceptor-mediated vasoconstriction by brimonidine in porcine ciliary arteries. Wikberg-Matsson, A., Simonsen, U. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
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