Type 3 muscarinic acetylcholine receptor stimulation is a determinant of endothelial barrier function and adherens junctions integrity: role of protein-tyrosine phosphatase 1B
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The main purpose of this study was to investigate whether type3 muscarinic acetylcholine receptor (M3R) dysfunctioninduced vascular hyperpermeability. Transwell system analysisshowed that M3R inhibition by selective antagonist4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP)and small interfering RNA both increased endothelialpermeability. Using coimmunoprecipitation and Western blotassay, we found that M3R inhibition increased VE-cadherinand β-catenin tyrosine phosphorylation without affecting theirexpression. Using PTP1B siRNA, we found that PTP1B wasrequired for maintaining VE-cadherin and β-catenin proteindephosphorylation. In addition, 4-DAMP suppressed PTP1Bactivity by reducing cyclic adenosine monophosphate (cAMP),but not protein kinase Cα (PKCα). These data indicate thatM3R preserves the endothelial barrier function through amechanism potentially maintaining PTP1B activity, keepingthe adherens junction proteins (AJPs) dephosphorylation.
Abstract
The main purpose of this study was to investigate whether type3 muscarinic acetylcholine receptor (M3R) dysfunctioninduced vascular hyperpermeability. Transwell system analysisshowed that M3R inhibition by selective antagonist4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP)and small interfering RNA both increased endothelialpermeability. Using coimmunoprecipitation and Western blotassay, we found that M3R inhibition increased VE-cadherinand β-catenin tyrosine phosphorylation without affecting theirexpression. Using PTP1B siRNA, we found that PTP1B wasrequired for maintaining VE-cadherin and β-catenin proteindephosphorylation. In addition, 4-DAMP suppressed PTP1Bactivity by reducing cyclic adenosine monophosphate (cAMP),but not protein kinase Cα (PKCα). These data indicate thatM3R preserves the endothelial barrier function through amechanism potentially maintaining PTP1B activity, keepingthe adherens junction proteins (AJPs) dephosphorylation.
참고문헌 (22)
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