Figure 6 - Prostaglandin F₂ (PGF₂)-induced protein kinase C (PKC) activation in LES tone and sustained contraction.

We have shown (data in brown and green) that maintenance of LES tone is PKC-dependent, and mediated in part by G_q linked to phosphatidylinositol-specific phospholipase C (PI-PLC) and by G_i3 linked to phosphatidylcholine-specific phospholipase (PC-PLC). The interrupted gray arrows represent a proposed contractile pathway for maintenance of tone and sustained contraction.² In sustained contraction receptors may activate G₁₃, and initiate a cascade involving activation of a guanine nucleotide exchange factor (Rho-GEF), RhoA, Rho kinase, and phospholipase D (PLD). PLD produces diacylglycerol (DAG), which activates PKC, causing contraction and may potentiate PLD activation. PLD is also activated by an adenosine diphosphate (ADP) ribosylation factor (ARF)-dependent pathway. The mechanisms of activation of Rho kinase–induced activation of PLD and of ARF activation are unknown. (Source: Harnett et al.,³ with permission from the American Physiological Society.)