Localization of α-adrenoceptors: JR Vane Medal Lecture.

UNLABELLED: This review is based on the JR Vane Medal Lecture presented at the BPS Winter Meeting in December 2011 by J.C. McGrath. A recording of the lecture is included as supporting information. It covers his laboratory's work from 1990 to 2010 on the localization of vascular α1 -adrenoceptors in native tissues, mainly arteries. MAIN POINTS: (i) α1 -adrenoceptors are present on several cell types in arteries, not only on medial smooth muscle, but also on adventitial, endothelial and nerve cells; (ii) all three receptor subtypes (α1 A , α1 B , α1 D ) are capable of binding ligands at the cell surface, strongly indicating that they are capable of function and not merely expressed. (iii) all of these cell types can take up an antagonist ligand into the intracellular compartments to which endocytosing receptors move; (iv) each individual subtype can exist at the cell surface and intracellularly in the absence of the other subtypes. As functional pharmacological experiments show variations in the involvement of the different subtypes in contractions of different arteries, it is concluded that the presence and disposition of α1 -adrenoceptors in arteries is not a simple guide to their involvement in function. Similar locations of the subtypes, even in different cell types, suggest that differences between the distribution of subtypes in model systems do not directly correlate with those in native tissues. This review includes a historical summary of the alternative terms used for adrenoceptors (adrenergic receptors, adrenoreceptors) and the author's views on the use of colours to illustrate different items, given his partial colour-blindness.