MAP-kinase dependent activation of kinin B1 receptor gene transcription after heat stress in rat vascular smooth muscle cells

The mechanism involved in the induction of kinin B-1 receptors in pathological situations is not completely defined. In this study, we evaluated whether p42/p44 mitogen activated protein (MAP) and p38 stress activated protein (SAP) kinases were implicated in the activation of the gene encoding for the B-1 receptor after heat stress in rat vascular smooth muscle cells (SMCs). Rat vascular SMCs were incubated with either vehicle. or 4(4-fluorophenyl)-2-(4 methylsulfinylphenyl)-5-(4pyridil)imidaz (SB 203580) (10 muM). a selective inhibitor of the p38 SAP kinase pathway or 2-(2amino-3-methoxyphenyl)4H-1-benzopyran-4-one (PD 98059) (25 muM), a selective inhibitor of the p42/p44 MAP kinase pathway and submitted or not to heat stress (42 degreesC, 20 min). Five hours later, B-1 receptor mRNA was detected using a semi-quantitative RT-PCR technique, In the meantime, we characterised p42/p44 MAP kinase activation after heat stress by immunodetection. A basal expression of B-1 receptor mRNA was detected in rat vascular SMCs. This expression was increased by heat stress. However, in cells previously incubated with either SE 203580 or PD 98059 and submitted to heat stress, this increase in B-1 receptor mRNA was not detected. Moreover. we showed by immunodetection that heat stress was followed by a transient phosphorylation of p42/p44 MAP kinases. In conclusion. both p42/p44 and p38 kinases play a crucial role in the mechanism leading to B-1 receptor mRNA induction after heat stress. (C) 2001 Elsevier Science B.V. All rights reserved.