Corticotropin-releasing factor receptors induce calcium mobilization through cross-talk with Gq- coupled receptors

Eric Gutknecht, Georges Vauquelin, F M Dautzenberg

Onderzoeksoutput: Articlepeer review

7 Citaten (Scopus)

Samenvatting

The crosstalk between muscarinic receptors and Corticotropin Releasing Factor (CRF) receptors was investigated by measuring evoked transient increases in cytosolic calcium concentration. HEK293 cells stably expressing human CRF type 1 (hCRF1) and type 2(a) (hCRF2(a)) receptors were stimulated with the muscarinic agonist carbachol and shortly after by a CRF agonist. Unexpectedly, this second response was enhanced when compared to stimulating naïve cells either with carbachol or CRF agonist only. Priming with 100 ?M carbachol increased the maximal CRF agonist response and shifted its concentration-response curve to the left to attain almost the same potency as for stimulating the production of the natural second messenger cyclic AMP (cAMP). Yet, priming did not affect CRF agonist-stimulated cAMP production itself.
Carbachol priming was not restricted to recombinant CRF receptors only since endogenously expressed ?-adrenergic receptors also started to produce a robust calcium signal. Without priming no such signal was observed. Similar findings were made in the human retinoblastoma Y79 cell line for endogenously expressed CRF1 receptors and the type 1 pituitary adenylate activating polypeptide (PACAP) receptors but not for the CRF2(a) receptors. This differentiation between CRF1 and CRF2 receptors was further supported by use of selective agonists and antagonists. The results suggest that stimulating a Gq-coupled receptor shortly before stimulating a Gs-coupled receptor may result in a parallel signaling event on top of the classical cAMP pathway.
Originele taal-2English
Pagina's (van-tot)1-9
Aantal pagina's9
TijdschriftEuropean Journal of Pharmacology
Volume642
Nummer van het tijdschrift1-3
StatusPublished - 10 sep 2010

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