Does the α1B-adrenoceptor regulate the other α1-adrenoceptor subtypes?

Laura Methven, John Christie McGrath. University of Glasgow, Glasgow, United Kingdom.

It has been proposed that through heterodimerisation, the α1B-adrenoceptor influences the cellular location and functional capabilities of the α1A- and α1D-adrenoceptor in isolated cells (Stanasila et al., 2003; Hague et al., 2004). The present study aimed to determine whether these interactions occur in native tissue.

First order mesenteric arteries from single knockouts (α1A-KO, α1B-KO, α1D-KO), double knockouts (α1A/B-KO, α1B/D-KO) and their wildtype controls were employed. The phenylephrine-induced response was compared across strains using wire myography. Confocal microscopy was used to compare fluorescent ligand binding of BODIPY-FL-prazosin (QAPB).

Comparison of strains showed that the phenylephrine-induced response in the wildtype was additive: a dominant α1A- and a small, but significant, α1D-component. Contraction was not altered by the absence of the α1B-adrenoceptor. Reduced fluorescence in all single knockouts suggests that all three α1-subtypes are present in the wildtype. Intracellular fluorescent ligand binding of the isolated α1A- and α1D- adrenoceptor was comparable to the wildtype.

In native tissue, the responses to α1-subtypes provide independent alternative signals for vascular regulation. Though only the α1A- and α1D-adrenoceptor mediate contraction in the mesenteric artery, fluorescent ligand binding suggests that all three α1-subtypes are present in this vessel. The cellular location of the α1A- or α1D-adrenoceptor is unchanged by presence of the α1B-adrenoceptor. In conclusion, the α1B-adrenoceptor does not regulate the vascular contraction or cellular location of the α1A- or α1D-adrenoceptor in native tissue.