PMID- 8866867 OWN - NLM STAT- MEDLINE DCOM- 19961213 LR - 20190512 IS - 0022-3751 (Print) IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 491 ( Pt 2) IP - Pt 2 DP - 1996 Mar 1 TI - Phospholipase A2 and protein kinase C contribute to myofilament sensitization to 5-HT in the rabbit mesenteric artery. PG - 447-53 AB - 1. Calcium (Ca2+, 0.1-100 microM) stimulated concentration-dependent contractions in small strips from the rabbit mesenteric artery in which the smooth muscle cells had been permeabilized with Staphylococcus aureus alpha-toxin. 2. 5-Hydroxytryptamine (5-HT) and phenylephrine, each in the presence of 10 microM guanosine 5'-triphosphate (GTP), concentration-dependently stimulated additional contractions in strips sub-maximally contracted by the presence of a buffered concentration of calcium (0.3 microM). All the additional contraction was abolished with the selective inhibitor of protein kinase C, Ro 31-8220 (10 microM). 3. Quinacrine (10-50 microM), an inhibitor of phospholipase A2, selectively inhibited the sensitization to 5-HT, but did not alter the sensitization to either phenylephrine or GTP. 4. Myofilament sensitization to calcium was mimicked by exogenous arachidonic acid (300 microM, in the presence of indomethacin, miconazole and BW755c) and the stable analogue of arachidonic acid, 5,8,11,14-eicosatetrayonic acid (ETYA, 100 microM), and in both cases did not require the additional presence of GTP. Ro 31-8220, but not quinacrine, reduced the sensitization to arachidonic acid by around 30%. 5. These results indicate that G protein-linked myofilament sensitization to calcium in the mesenteric artery that follows the activation of 5-HT receptors, but not alpha 1-receptors, involves phospholipase A2. The sensitization stimulated by each of these different receptors, and a component of the response to arachidonic acid, also appears to involve the activation of protein kinase C. FAU - Parsons, S J AU - Parsons SJ AD - Department of Pharmacology, University of Bristol, UK. FAU - Sumner, M J AU - Sumner MJ FAU - Garland, C J AU - Garland CJ LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 1WS297W6MV (Phenylephrine) RN - 333DO1RDJY (Serotonin) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.1.1.4 (Phospholipases A2) RN - H0C805XYDE (Quinacrine) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*pharmacology MH - Dose-Response Relationship, Drug MH - Female MH - Mesenteric Arteries/*drug effects MH - Phenylephrine/pharmacology MH - Phospholipases A/*pharmacology MH - Phospholipases A2 MH - Protein Kinase C/*pharmacology MH - Quinacrine/pharmacology MH - Rabbits MH - Serotonin/*pharmacology PMC - PMC1158738 EDAT- 1996/03/01 00:00 MHDA- 1996/03/01 00:01 PMCR- 1996/03/01 CRDT- 1996/03/01 00:00 PHST- 1996/03/01 00:00 [pubmed] PHST- 1996/03/01 00:01 [medline] PHST- 1996/03/01 00:00 [entrez] PHST- 1996/03/01 00:00 [pmc-release] AID - 10.1113/jphysiol.1996.sp021228 [doi] PST - ppublish SO - J Physiol. 1996 Mar 1;491 ( Pt 2)(Pt 2):447-53. doi: 10.1113/jphysiol.1996.sp021228.