Study of the activation mechanism of human GRF(1-29)NH2 on rat mast cell histamine release.
Human growth releasing factor (GRF) (1-29)NH2 releases histamine from pleural and peritoneal rat mast cells by a non cytotoxic and non immunological mechanism. Pretreatment of cells with pertussis toxin markedly inhibits the secretion, suggesting a possible function of a Gi-protein in the activation pathway. In order to determine the role of cAMP on GRF mediated secretion, mast cells were preincubated with isobutylmethylxanthine (IBMX) or cholera toxin, since both drugs greatly and enhance cAMP levels. IBMX inhibits mediator secretion while, in contrast, cholera toxin is ineffective to modify histamine release. The PKC activator TPA amplifies the response of mast cells to human GRF, shifting the dose-response curve to the left. The pretreatment of mast cells with the phosphatase inhibitor okadaic acid exerts no effect on the dose-response function curve to GRF. The response to human GRF does not depend on extracellular calcium, but there is a good correlation between the percent of histamine released and 45calcium uptake. The kinetic of calcium uptake is fast, maximum uptake being reached in 30 seconds.
Estévez
M D
MD
Departamento de Farmacología, Facultad de Veterinaria, Lugo, Spain.
Alfonso
A
A
Vieytes
M R
MR
Louzao
M C
MC
Botana
L M
LM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D037342:Pertussis Toxin; D010994:Pleura / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017337:Sermorelin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D017337:Sermorelin; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine