Comparison of signalling mechanisms involved in rat mesenteric microvessel contraction by noradrenaline and sphingosylphosphorylcholine

We have compared the signalling mechanisms involved in the pertussis toxin‐sensitive and ‐insensitive contraction of rat isolated mesenteric microvessels elicited by sphingosylphosphorylcholine (SPC) and noradrenaline (NA), respectively. The phospholipase D inhibitor butan‐1‐ol (0.3%), the store‐operated Ca 2+ channel inhibitor SK>F 96,365 (10 μ M ), the tyrosine kinase inhibitor genistein (10 μ M ), and the src inhibitor PP2 (10 μ M ) as well as the negative controls (0.3% butan‐2‐ol and 10 μ M diadzein and PP3) had only little effect against either agonist. Inhibitors of phosphatidylinositol‐3‐kinase (wortmannin and LY 294,002, 10 μ M each) or of mitogen‐activated protein kinase kinase (PD 98,059 and U 126, 10 μ M each) did not consistently attenuate NA‐ and SPC‐induced contraction as compared to their vehicles or negative controls (LY 303,511 or U 124). The phospholipase C inhibitor U 73,122 (10 μ M ) markedly inhibited the SPC‐ and NA‐induced contraction (70% and 88% inhibition of the response to the highest NA and SPC concentration, respectively), whereas its negative control U 73,343 (10 μ M ) caused only less than 30% inhibition. The rho‐kinase inhibitors Y 27,632 (10 μ M ) and fasudil (30 μ M ) caused a rightward‐shift of the NA concentration‐response curve by 0.7–0.8 log units and reduced the response to 10 μ M SPC by 88% and 83%, respectively. These data suggest that SPC and NA, while acting on different receptors coupling to different G‐protein classes, elicit contraction of rat mesenteric microvessels by similar signalling pathways including phospholipase C and rho‐kinase.British Journal of Pharmacology (2003) 138 , 261–271. doi: 10.1038/sj.bjp.0705028