Phenylephrine-Induced Contraction in Guinea Pig Thoracic Aorta Is Triggered by Stimulation of α-Adrenoceptors Functionally Coupled with Store-Operated Ca Channels and Voltage-Dependent Ca Channels.

We examined whether the α-adrenoceptor (AR), which shows low affinity (pA < 9) for prazosin (an α-AR antagonist) and high affinity (pA ≈ 10) for tamsulosin/silodosin (α-AR antagonists), is involved in phenylephrine-induced contractions in the guinea pig (GP) thoracic aorta (TA). Intracellular signaling induced by α-AR activation was also examined by focusing on Ca influx pathways. Tension changes of endothelium-denuded TAs were isometrically recorded and mRNA encoding α-ARs/Ca channels and their related molecules were measured using RT-quantitative PCR. Phenylephrine-induced contractions were competitively inhibited by prazosin/tamsulosin, and their pA 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 value being 9.48. In contrast, phenylephrine-induced contractions were not substantially suppressed by L-765314 (an α-AR antagonist), BMY 7378 (an α-AR antagonist), yohimbine, and idazoxan (α-AR antagonists). Phenylephrine-induced contractions were markedly inhibited by YM-254890 (a Gq protein inhibitor) or removal of extracellular Ca, and partially inhibited by verapamil (a voltage-dependent Ca channel (VDCC) inhibitor). The residual contractions in the presence of verapamil were slightly inhibited by LOE 908 (a receptor-operated Ca channel (ROCC) inhibitor) and strongly inhibited by SKF-96365 (a store-operated Ca channel (SOCC) and ROCC inhibitor). Among the mRNA encoding α-ARs/SOCC-related molecules, α-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-AR, followed by activation of SOCCs and VDCCs.