Activation of the p38 and p42/p44 mitogen-activated protein kinase families by the histamine H(1) receptor in DDT(1)MF-2 cells.
1. The mitogen-activated protein kinases (MAPKs) consist of the p42/p44 MAPKs and the stress-activated protein kinases, c-Jun N-terminal kinase (JNK) and p38 MAPK. In this study we have examined the effect of histamine H(1) receptor activation on MAPK pathway activation in the smooth muscle cell line DDT(1)MF-2. 2. Histamine stimulated time and concentration-dependent increases in p42/p44 MAPK activation in DDT(1)MF-2 cells. Responses to histamine were inhibited by the histamine H(1) receptor antagonist mepyramine (K(D) 3.5 nM) and following pre-treatment with pertussis toxin (PTX; 57% inhibition). 3. Histamine-induced increases in p42/p44 MAPK activation were blocked by inhibitors of MAPK kinase 1 (PD 98059), tyrosine kinase (genistein and tyrphostin A47), phosphatidylinositol 3-kinase (wortmannin and LY 294002) and protein kinase C (Ro 31-8220; 10 microM; 41% inhibition). Inhibitors of Src tyrosine kinase (PP2) and the epidermal growth factor tyrosine kinase (AG1478) were without effect. Removal of extracellular Ca(2+), chelation of intracellular Ca(2+) with BAPTA and inhibition of focal adhesion assembly (cytochalasin D) had no significant effect on histamine-induced p42/p44 MAPK activation. 4. Histamine stimulated time and concentration-dependent increases in p38 MAPK activation in DDT(1)MF-2 cells but had no effect on JNK activation. Histamine-induced p38 MAPK activation was inhibited by pertussis toxin (74% inhibition) and the p38 MAPK inhibitor SB 203580 (95% inhibition). 5. In summary, we have shown the histamine H(1) receptor activates p42/p44 MAPK and p38 MAPK signalling pathways in DDT(1)MF-2 smooth muscle cells. Interestingly, signalling to both pathways appears to involve histamine H(1) receptor coupling to G(i)/G(o)-proteins.
Robinson
A J
AJ
Department of Life Sciences, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS.
Dickenson
J M
JM
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D014649:Vas Deferens; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D002118:Calcium; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006632:Histamine; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D011725:Pyridines; D011969:Receptors, Histamine H1; D010566:Virulence Factors, Bordetella; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580