Characterization of histamine-induced catecholamine secretion from bovine adrenal medullary chromaffin cells.
Histamine activation of H1 receptors stimulates 3H release from cultured bovine adrenal chromaffin cells preloaded with [3H]noradrenaline. The initial (1-min) release induced by a high concentration of histamine was unaffected by the removal of extracellular Ca2+, whereas the more sustained response (10 min) was largely inhibited. In contrast, release induced by nicotine was dependent on extracellular Ca2+ at all times. The protein kinase inhibitor staurosporine inhibited both the initial and sustained (10-min) phases of histamine-induced release (IC50 in the region of 200 nM) but was ineffective against a direct depolarizing stimulus (56 mM K+). In contrast, the calmodulin antagonist trifluoperazine was equally effective against both stimuli. These data indicate that although a staurosporine-sensitive event (perhaps involving protein kinase C) is essential for coupling histamine receptor activation to the release processes, it is not essential for exocytosis itself. A further distinction between histamine- and depolarization-induced release was demonstrated by the differential effect of the guanine nucleotide-binding protein inhibitor pertussis toxin. Pretreatment with pertussis toxin (0.1 microgram/ml for 16 h) enhanced depolarization-induced release by approximately 1.5-fold. This pertussis toxin pretreatment was, however, approximately twofold as effective in potentiating histamine-evoked release. Thus, the characteristics of the histaminergic response are distinct from those of a depolarizing stimulus, perhaps indicating the involvement of different mechanisms in the release process.
Bunn
S J
SJ
Neuroscience Group, Faculty of Medicine, University of Newcastle, New South Wales, Australia.
Boyd
T L
TL
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D037342:Pertussis Toxin; D047428:Protein Kinase Inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002395:Catecholamines; D047428:Protein Kinase Inhibitors; D010566:Virulence Factors, Bordetella; D006632:Histamine; D037342:Pertussis Toxin; D002118:Calcium