Thrombin and melittin activate phospholipase C in human HaCaT keratinocytes.
Following the activation of specific receptors, phospholipase C has been shown to cleave the membrane phospholipid phosphatidylinositol bisphosphate into the 2nd messengers inositol 1,4,5-trisphosphate and diacylglycerol. Both 2nd messengers contribute to the regulation of cellular proliferation. The receptor for bradykinin is coupled to this pathway in keratinocytes, but knowledge about other activators of phospholipase C is limited. Additional mediators and agents were therefore examined regarding their ability to activate phospholipase C in HaCaT keratinocytes. Analysis for 3H-inositol phosphates was performed by anion-exchange HPLC. Thrombin and melittin induced a time- and dose-dependent release of inositol 1,4,5-trisphosphate. Several other mediators examined such as angiotension II, neurotensin, C3a, pituitary adenylate cyclase activating peptide, phenylephrin, and prostaglandin E2, did not induce the formation of inositol phosphates. In view of the mitogenic activity and the increased formation of thrombin after tissue injury, the coupling of the thrombin receptor to phospholipase C in HaCaT keratinocytes suggests a role of this protease in epidermal wound healing.
Haase
I
I
Department of Dermatology, Virchow Clinic, Humboldt University, Berlin, FRG.
Czarnetzki
B M
BM
Rosenbach
T
T
D000804:Angiotensin II / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D015926:Complement C3a / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008555:Melitten / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology; D009496:Neurotensin / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D015290:Second Messenger Systems; D013917:Thrombin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*
C495401:ADCYAP1 protein, human; D007295:Inositol Phosphates; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D000804:Angiotensin II; D010656:Phenylephrine; D008555:Melitten; D009496:Neurotensin; D015926:Complement C3a; D010738:Type C Phospholipases; D013917:Thrombin; D015232:Dinoprostone; D001920:Bradykinin