The effect of sphingosine-1-phosphate on colonic smooth muscle contractility: Modulation by TNBS-induced colitis
Fig 6
Proposed mechanism of S1P induced contraction in control and colitic colon.
In control colon S1P activates S1PR1 and S1PR2 and induce contractions that are dependent on calcium influx via L-type calcium channels, calcium release from the sarcoplasmic reticulum and calcium sensitization pathways including PKC and Rho kinase (A). In colitic colon however S1P induces larger contractions via S1PR2 that are independent of calcium influx through L-type calcium channels yet it involves intracellular calcium release and calcium sensitization pathways (B). The contribution of these pathways however appears to be different in control and inflamed colon segments. Whereas the blockade of a single pathway completely abolishes the response to S1P in control segments, S1P induced contractions appear to be salvaged by other pathways in inflamed colon segments. Eradication of S1P induced contraction in inflamed colon require simultaneous blockade of intracellular calcium release (SERCA) and calcium sensitization pathways (PKC and Rho kinase).