The possible role of histamine-mediated cAMP formation as a link between H2-receptor stimulation and ultrastructural changes in guinea-pig oxyntic cells.
Guinea-pig oxyntic cell tubulin has been isolated and in vitro aggregation has been studied. The spontaneous assembly of isolated tubulin was significantly accelerated and increased by 1 mmol/l GTP. Histamine and forskolin increased tubulin polymerization only when detergent dispersed oxyntic cells or crude membranes were added. The forskolin response occurred very rapidly with an EC50 of approximately 30 mumol/l and did not require GTP. Histamine promoted tubulin aggregation with an EC50 of about 5 mumol/l only in the presence of GTP. Ranitidine completely inhibited the effects of histamine. From these data it is suggested that, in the oxyntic cell, histamine H2-receptor activated adenylate cyclase and the corresponding increase in cAMP play a role in eliciting characteristic ultrastructural changes by initiating formation of microtubules as a first step in the cascade of events leading to an increase in the secretory surface area.
Albinus
M
M
Department of Pharmacology, University of Tübingen, FRG.
Armbruckner
L
L
Klein
S
S
Maier
R
R
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011899:Ranitidine / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D011970:Receptors, Histamine H2; D014404:Tubulin; D005576:Colforsin; D006632:Histamine; D006160:Guanosine Triphosphate; D011899:Ranitidine; D000242:Cyclic AMP