Skip to main content
. Author manuscript; available in PMC: 2007 Jun 19.
Published in final edited form as: Biochem Pharmacol. 2007 Jan 7;73(8):1146–1156. doi: 10.1016/j.bcp.2007.01.001

Figure 9. Proposed MAPK-PLA2-PGE2-EP3R signaling pathway involved in the H3R-mediated attenuation of NE exocytosis in cardiac sympathetic nerve terminals.

Figure 9

Stimulation of H3R on sympathetic nerve endings results in the Gβγi-mediated intraneuronal activation of the MAPK cascade. MAPK activation phosphorylates cPLA2 which is then translocated to the cellular membrane, with the consequent formation of arachidonic acid (AA) from membrane phospholipids (PL), and the subsequent production of PGE2 via cyclooxygenase (COX). PGE2 activates EP3R on the neuronal membrane, and the Gβγi subunit of EP3R inhibits Ca2+ entry, thus attenuating NE exocytosis. The Gβγi subunit of H3R may also directly inhibit Ca2+ entry without MAPK intervention.