Phospholipase D1 is involved in α1-adrenergic contraction of murine vascular smooth muscle

(1)-Adrenergic stimulation increases blood vessel tone in mammals. This process involves a number of intracellular signaling pathways that include signaling via phospholipase C, diacylglycerol (DAG), and protein kinase C. So far, it is not certain whether signaling via phospholipase D (PLD) and PLD-derived DAG is involved in this process. We asked whether PLD participates in the (1)-adrenergic-mediated signaling in vascular smooth muscle. (1)-Adrenergic-induced contraction was assessed by myography of isolated aortic rings and by pressure recordings using the hindlimb perfusion model in mice. The effects of the PLD inhibitor 1-butanol (IC50 0.15 vol%) and the inactive congener 2-butanol were comparatively studied. Inhibition of PLD by 1-butanol reduced specifically the (1)-adrenergic-induced contraction and the (1)-adrenergic-induced pressure increase by 10 and 40% of the maximum, respectively. 1-Butanol did not influence the aortic contractions induced by high extracellular potassium, by the thromboxane analog U46619, or by a phorbol ester. The effects of 1-butanol were absent in mice that lack PLD1 (Pld1(-/-) mice) or that selectively lack the Ca(V)1.2 channel in smooth muscle (sm-Ca(V)1.2(-/-) mice) but still present in the heterozygous control mice. (1)-Adrenergic contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the (1)-adrenergic-induced Ca(V)1.2 channel activity.Wegener, J. W., Loga, F., Stegner, D., Nieswandt, B., Hofmann, F. Phospholipase D1 is involved in (1)-adrenergic contraction of murine vascular smooth muscle.