Activation of mitogen-activated protein kinase and arachidonate release via two G protein-coupled receptors expressed in the rat hippocampus.

ABSTRACT

Platelet-activating factor and somatostatin receptors, two G protein-coupled receptors expressed in the rat hippocampus, were analyzed for the downstream signaling pathways in Chinese hamster ovary cells stably expressing each receptor. Ligand stimulation to each CHO cell line induced (1) inhibition of forskolin-induced accumulation of cAMP, (2) arachidonate release, and (3) activation of mitogen-activated protein kinase and MAP kinase kinase. In contrast, inositol phosphate breakdown was seen only in the PAF-stimulated CHO cells. The induction of these signals accompanied no detectable Ras activation. Suppression of the signals by pertussis toxin was almost complete for the somatostatin receptor but partial for the PAF receptor, suggesting that the somatostatin receptor couples only with PTX-sensitive G protein, while the PAF receptor couples with both PTX-sensitive and -insensitive G proteins. A model of G protein-mediated signaling pathways was proposed in which the signals from Gi and those from Gq converge at MAP kinase kinase and lead to arachidonate release. The present system using CHO cells is useful for analyzing signaling pathways from G proteins to MAP kinase kinase and will thereby provide clues for understanding the mechanisms underlying the physiological and pathological events mediated by PAF, somatostatin, and other G protein-coupled receptors in the central nervous system and other tissues.