Comparison of signalling mechanisms involved in rat mesenteric microvessel contraction by noradrenaline and sphingosylphosphorylcholine.
1 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. 2 The phospholipase D inhibitor butan-1-ol (0.3%), the store-operated Ca(2+) channel inhibitor SK>F 96,365 (10 microM), the tyrosine kinase inhibitor genistein (10 microM), and the src inhibitor PP2 (10 microM) as well as the negative controls (0.3% butan-2-ol and 10 microM diadzein and PP3) had only little effect against either agonist. 3 Inhibitors of phosphatidylinositol-3-kinase (wortmannin and LY 294,002, 10 microM each) or of mitogen-activated protein kinase kinase (PD 98,059 and U 126, 10 microM each) did not consistently attenuate NA- and SPC-induced contraction as compared to their vehicles or negative controls (LY 303,511 or U 124). 4 The phospholipase C inhibitor U 73,122 (10 microM) 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 microM) caused only less than 30% inhibition. 5 The rho-kinase inhibitors Y 27,632 (10 microM) and fasudil (30 microM) caused a rightward-shift of the NA concentration-response curve by 0.7-0.8 log units and reduced the response to 10 microM SPC by 88% and 83%, respectively. 6 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.
Altmann
Christoph
C
Department of Pharmacology, University of Essen, 45122 Essen, Germany.
Steenpass
Veronika
V
Czyborra
Peter
P
Hein
Peter
P
Michel
Martin C
MC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D013110:Sphingosine; D009638:Norepinephrine