Presence of functionally active protease-activated receptors 1 and 2 in myenteric glia

Rosario Garrido, Bradley Segura, Weizhen Zhang, Michael Mulholland

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27 Scopus citations

Abstract

Protease-activated receptors (PARs) belong to the family of membrane receptors coupled to G-proteins; their presence is reported in a wide variety of cells. The object of this study was to demonstrate the presence of PAR-1 and PAR-2 in myenteric glia of the guinea pig, and to elucidate the cellular mechanisms that are triggered upon receptor activation. Thrombin and PAR-1 agonist peptide (PARP-1) activate PAR-1 with a maximum mean ± SEM change in intracellular calcium concentration with respect to basal level (Δ[Ca2+]i) of 183 ± 18 nM and 169 ± 6 nM, respectively. Trypsin and PAR-2 agonist peptide (PARP-2) activate PAR-2 with a maximum Δ[Ca2+]i of 364 ± 28 nM and 239 ± 19 nM, respectively. Inhibition of phospholipase C by U73312 (1 μM) decreased the Δ[Ca2+]i due to PAR-1 activation from 167 ± 10 nM to 87 ± 6 nM. The PAR-2-mediated Δ[Ca2+]i decreased from 193 ± 10 nM to 124 ± 8 nM when phospholipase C activity was inhibited. Blockade of sphingosine kinase with dimethylsphingosine (1 μM) decreased the Δ[Ca2+]i due to PAR-2 activation from 149 ± 19 nM to 67 ± 1 nM, but did not influence the PAR-1-mediated Δ[Ca2+]i. PAR-1 and PAR-2 were localized in myenteric glia by immunolabeling. Our results indicate that PAR-1 and PAR-2 are present in myenteric glia of the guinea pig, and their activation leads to increases in intracellular calcium via different signal transduction mechanisms that involve activation of phospholipase C and sphingosine kinase.

Original languageEnglish (US)
Pages (from-to)556-564
Number of pages9
JournalJournal of Neurochemistry
Volume83
Issue number3
DOIs
StatePublished - Nov 2002

Keywords

  • Calcium
  • Enteric glia
  • Protease-activated receptors
  • Signal transduction

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