title: Phospholipase D1 is involved in α1-adrenergic contraction of murine vascular smooth muscle.
abstract: α1-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 α1-adrenergic-mediated signaling in vascular smooth muscle. α1-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 α1-adrenergic-induced contraction and the α1-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 CaV1.2 channel in smooth muscle (sm-CaV1.2(-/-) mice) but still present in the heterozygous control mice. α1-Adrenergic contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the α1-adrenergic-induced CaV1.2 channel activity.
authors.affiliation: 1For 923, Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, 80802 München, Germany. joerg.wegener@mytum.de.
authors.forename: Jörg W
authors.initials: JW
authors.lastname: Wegener
authors.forename: Florian
authors.initials: F
authors.lastname: Loga
authors.forename: David
authors.initials: D
authors.lastname: Stegner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010739:Phospholipase D / Q000235:genetics / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D010739:Phospholipase D; C106801:phospholipase D1; D002118:Calcium
keywords: CaV1.2 Ca2+ channel; U46619; blood pressure; intracellular signaling