Phospholipase D1 is involved in α‐adrenergic contraction of murine vascular smooth muscle

α 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 α 1 ‐adrenergic‐mediated signaling in vascular smooth muscle. α 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 (IC 50 0.15 vol%) and the inactive congener 2‐butanol were comparatively studied. Inhibition of PLD by 1‐butanol reduced specifically the α 1 ‐adrenergic‐induced contraction and the α 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. α 1 ‐Adrenergic contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the α 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 α 1 ‐adrenergic contraction of murine vascular smooth muscle. FASEB J. 28, 1044–1048 (2014). www.fasebj.org