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Comparison of signalling mechanisms involved in rat mesenteric microvessel contraction by noradrenaline and sphingosylphosphorylcholine
Author(s) -
Altmann Christoph,
Steenpaß Veronika,
Czyborra Peter,
Hein Peter,
Michel Martin C
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705028
Subject(s) - wortmannin , pertussis toxin , endocrinology , contraction (grammar) , phospholipase c , bisindolylmaleimide , medicine , rho kinase inhibitor , protein kinase c , chemistry , tyrosine kinase inhibitor , phosphatidylinositol , muscle contraction , kinase , biology , rho associated protein kinase , g protein , receptor , biochemistry , cancer
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