We examined whether the α 1L -adrenoceptor (AR), which shows low affinity (pA 2 < 9) for prazosin (an α 1 -AR antagonist) and high affinity (pA 2 ≈ 10) for tamsulosin/silodosin (α 1A -AR antagonists), is involved in phenylephrine-induced contractions in the guinea pig (GP) thoracic aorta (TA). Intracellular signaling induced by α 1L -AR activation was also examined by focusing on Ca 2 influx pathways. Tension changes of endothelium-denuded TAs were isometrically recorded and mRNA encoding α-ARs/Ca 2 channels and their related molecules were measured using RT-quantitative PCR. Phenylephrine-induced contractions were competitively inhibited by prazosin/tamsulosin, and their pA 2 value were calculated to be 8.53/9.74, respectively. These contractions were also inhibited by silodosin concentration-dependently. However, the inhibition was not competitive fashion with the apparent pA 2 value being 9.48. In contrast, phenylephrine-induced contractions were not substantially suppressed by L-765314 (an α 1B -AR antagonist), BMY 7378 (an α 1D -AR antagonist), yohimbine, and idazoxan (α 2 -AR antagonists). Phenylephrine-induced contractions were markedly inhibited by YM-254890 (a Gq protein inhibitor) or removal of extracellular Ca 2 , and partially inhibited by verapamil (a voltage-dependent Ca 2 channel (VDCC) inhibitor). The residual contractions in the presence of verapamil were slightly inhibited by LOE 908 (a receptor-operated Ca 2 channel (ROCC) inhibitor) and strongly inhibited by SKF-96365 (a store-operated Ca 2 channel (SOCC) and ROCC inhibitor). Among the mRNA encoding α-ARs/SOCC-related molecules, α 1A -AR (Adra1a)/Orai3, Orai1, and Stim2 were abundant in this tissue. In conclusion, phenylephrine-induced contractions in the GP TA can be triggered by stimulation of Gq protein-coupled α 1L -AR, followed by activation of SOCCs and VDCCs.
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