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Novel Ca 2+ signaling pathway for AVP mediated vasoconstriction
Author(s) -
Henderson Kyle K,
Byron Kenneth L
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1444-a
Subject(s) - vasopressin , vasoconstriction , protein kinase c , calphostin c , vascular smooth muscle , endocrinology , medicine , chemistry , signal transduction , vasopressin receptor , receptor , biology , microbiology and biotechnology , antagonist , smooth muscle
[Arg 8 ]‐vasopressin (AVP) is a peptide hormone which exerts vasoconstrictor effects by binding to V 1a vasopressin receptors on vascular smooth muscle cells (VSMC). This effect is attributed to activation of phosphoinositidase C (PIC) and consequent release of Ca 2+ from the sarcoplasmic reticulum. Interestingly, half‐maximal activation of PIC requires nanomolar AVP concentrations, whereas circulating AVP concentrations rarely exceed 100pM. Using cultured VSMC, we previously identified a novel Ca 2+ signaling pathway activated by 10–100pM AVP. This Ca 2+ signaling pathway is distinguished from the PIC pathway by its dependence upon protein kinase C (PKC) activation and L‐type voltage‐sensitive Ca 2+ channels (VSCC). In the present study, we tested the hypothesis that picomolar AVP concentrations would induce PKC‐ and VSCC‐dependent vasoconstriction in isolated pressurized rat mesenteric arteries. AVP (10 −14 to 10 −6 M) induced a concentration‐dependent constriction of arteries that was reversible with a V 1a vasopressin receptor antagonist. 30pM AVP induced significant vasoconstriction (~45% of maximum), which was prevented by PKC inhibition with calphostin‐C (250nM) or Ro‐31–8220 (1μM) as well as by blockade of VSCC with verapamil (10μM). In contrast, maximal vasoconstriction induced by 10nM AVP was insensitive to either PKC inhibition or blockade of VSCC. These results suggest that two dose‐dependent signaling pathways exist for AVP‐induced vasoconstriction. Accordingly, we conclude that the vasoconstrictor actions of picomolar AVP within the systemic circulation may be dependent upon the novel Ca 2+ signaling pathway involving PKC activation and L‐type VSCC. NIH RO1‐HL070670 and Falk Fellowship