In vivo effects of tunicamycin on the secretory processes of rat parotid glands.
The morphological and functional effects of tunicamycin were studied in rat parotid glands at the stage of the reformation of secretory granules following secretory stimulation by isoproterenol. Tunicamycin inhibited the incorporation of (3H)-mannose into the acid-insoluble fraction but had no effect on total protein synthesis as determined by the incorporation of (14C)-leucine. Thus the administration of tunicamycin in vivo inhibits the synthesis of mannose-rich glycoproteins in a manner similar to that in an in vitro system. The ultrastructure of the acinar cell showed little change following treatment with this drug, except that the number of reaccumulated secretory granules was greater than in the control. Amylase secretion stimulated by isoproterenol was inhibited in tunicamycin-treated cells, but did not decrease following treatment with N6,2'-O-dibutyryladenosine 3'-5'-cyclic monophosphate, a secretory stimulator bypassing the beta-receptor. A radio-receptor assay using (3H)-dihydroalprenolol and direct localization using the fluorescent beta-adrenergic blocker 9-amino-acridin-propranolol showed a marked reduction in the binding activity of beta-receptor following treatment with tunicamycin. Thus the inhibition of N-linked glycosylation appears to produce profound effects on the beta-adrenergic receptor-adenylate cyclase complex of acinar cells, although the steps of the transport and the exocytotic discharge of secretory materials are not affected.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000681:Amylases / Q000378:metabolism; D000818:Animals; D006023:Glycoproteins / Q000096:biosynthesis; D008297:Male; D008854:Microscopy, Electron; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
D006023:Glycoproteins; D011943:Receptors, Adrenergic, beta; D014415:Tunicamycin; D000681:Amylases; D000262:Adenylyl Cyclases