Removal of the α1B-adrenoceptor Uncovers an α1D Component in Mesenteric Resistance Arteries

McBride, M., Daly, C.J. , Tsujimoto, G. and McGrath, J.C. (2003) Removal of the α1B-adrenoceptor Uncovers an α1D Component in Mesenteric Resistance Arteries. XXXII Congress of the Spanish Society of Physiological Sciences International Joint Meeting with The Physiological Society, Puerto de la Cruz, Tenerife, 13-17 Feb 2003.

Abstract

α1A-Adrenoceptors play the dominant vasoconstrictor role in mouse mesenteric resistance arteries (Daly et al. 2002). We now analyse the receptor population remaining after removal of the α1B or α1D-adrenoceptor (Tanoue et al. 2002) by receptor knockouts (KO). Sixteen-month-old male (22-31 g) (C57Bl(WT), α1BKO, α1DKO) mice were killed by CO2 and mesenteric arteries isolated. Rings (2 mm) were mounted in Krebs at 37 °C on a wire myograph. Cumulative phenylephrine (α1 agonist) was administered alone or in the presence of 5-methylurapadil (5MeU) (α1A-selective antagonist; 1 X 10-7 M) or BMY7378 (α1D-selective antagonist; 1 X 10-7 M), concentrations chosen for subtype selectivity. α1B and α1DKOs had greater maxima than controls. α1D knockout had reduced sensitivity to phenylephrine compared to WT and α1BKO (Table 1). 5MeU caused a rightward shift in all three strains. However in the α1BKO the response became biphasic (Fig. 1). This second component is abolished by BMY7378, indicating the α1D-adrenoceptor. BMY7378 failed to shift the response further in either the α1DKO or in WT. Removal of either of the ‘minor’ α1-adrenoceptor subtypes (α1B or α1D) affects the contractile function of mesenteric resistance arteries. In the absence of α1D receptors, the maximum is greater (unexplained) but sensitivity to phenylephrine is decreased (suggesting an α1D response in WT). Absence of α1B-adrenoceptor increases sensitivity to α1D; a 5MeU-resistant, BMY7378-sensitive component appears. This illustrates that removal of one α1 subtype can alter the functional response via the remaining receptor population. The presence of multiple α1 subtypes that has dogged pharmacological analysis is confirmed. The α1D subtype, dominant in conducting arteries, contributes a minor component in these small ‘resistance’ arteries that might be upregulated by modulatory or pathophysiological factors. M.McB. is supported by the British Heart Foundation. Our group is a member of the EC FP5 project ‘Vascan’ (QLG1-CT-1999-00084).

• Item Type: Conference or Workshop Item
• Additional Information: Poster Communication.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGrath, Professor John and Daly, Professor Craig
• Authors: McBride, M., Daly, C.J., Tsujimoto, G., and McGrath, J.C.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences