Phospholipase D (PLD) Signaling Pathway is involved in the Postjunctional Interactions between the Sympathetic Cotransmitters ATP and Norepinephrine (NE)

• Published in: The FASEB journal 2006-03, Vol.20 (4), p.A243-A244
• Main Authors: Todorov, Latchezar Dimitrov, Mihaylova‐Todorova, Svetlana Trifonova, Choe, Sophie, Westfall, David P
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A243-d

Previously we have demonstrated that NE amplifies the smooth muscle contractile response evoked by its cotransmitter ATP via a mechanism that involves protein tyrosine phosphorylation. In this study, we have examined the effects of the PLD inhibitor 1‐butanol relative to its inactive analogues 2‐butanol and tert‐butanol on the facilitation of the purinergic contractions of the guinea pig vas deferens evoked by either NE or sodium orthovanadate (SOV). The robust increase of the contractile responses evoked by a single impulse of electrical field stimulation (EFS) or exogenous ATP in the presence of NE or SOV was abolished in the presence of 1‐butanol. Application of 2‐butanol or tert‐butanol did not change the amplitude of the contractile responses evoked by either EFS or exogenous ATP in the presence of NE or SOV. However, an addition of 1‐butanol to either 2‐butanol or tert‐butanol treated tissues eliminated the NE‐ and SOV‐induced facilitation of the purinergic contraction of the vas deferens. The removal of 1‐butanol restored the facilitation of the purinergic contractions. Exogenously applied phosphatidic acid (PA), a product of the PLD hydrolysis of phosphatidyl choline produced a concentration‐dependent increase of the amplitude of the EFS‐induced contractile responses of the vas deferens. Based on this evidence we conclude that NE acting via postjunctional alpha 2 ‐adrenergic receptors activates a PLD signaling pathway that modulates the responsiveness of the smooth muscle to the actions of its cotransmitter ATP. Supported by NIH HL38126.