Phospholipase C-mediated signalling is not required for histamine-induced catecholamine secretion from bovine chromaffin cells.
A possible role for signalling through phospholipase C in histamine-induced catecholamine secretion from bovine adrenal chromaffin cells has been investigated. Secretion evoked by histamine over 10 min was not prevented by inhibiting inositol-1,4,5-trisphosphate receptors with 2-APB, by blocking ryanodine receptors with a combination of ryanodine and caffeine, or by depleting intracellular Ca(2+) stores by pretreatment with thapsigargin. Inhibition of protein kinase C with Ro31-8220 also failed to reduce secretion. Inhibition of phospholipase C with ET-18-OCH(3) reduced both histamine- and K(+) -induced inositol phosphate responses by 70-80% without reducing their secretory responses. Stimulating phospholipase C with Pasteurella multocida toxin did not evoke secretion or enhance the secretory response to histamine. The secretory response to histamine was little affected by tetrodotoxin or by substituting extracellular Na(+) with N -methyl-d-glucamine(+) or choline(+), or by substituting external Cl(-) with nitrate(-). Blocking various K(+) channels with apamin, charybdotoxin, Ba(2+), tetraethylammonium, 4-aminopyridine, tertiapin or glibenclamide failed to reduce the ability of histamine to evoke secretion. These results indicate that histamine evokes secretion by a mechanism that does not require inositol-1,4,5-trisphosphate-mediated mobilization of stored Ca(2+), diacylglycerol-mediated activation of protein kinase C, or activation of phospholipase C. The results are consistent with histamine acting by depolarizing chromaffin cells through a phospholipase C-independent mechanism.
Donald
Amanda N
AN
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Wallace
Damian J
DJ
McKenzie
Sacha
S
Marley
Philip D
PD
D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015220:Calcium Channels; D002395:Catecholamines; D004791:Enzyme Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; C062258:Pasteurella multocida toxin; D026902:Potassium Channel Blockers; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D013779:Tetrodotoxin; D006632:Histamine; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium