Casein secretion in mammary tissue: tonic regulation of basal secretion by protein kinase A.
Despite its quantitative importance in the secretion of lactoproteins, little is known about the triggering and control mechanisms that initiate, regulate and terminate the operation of the basal pathway of lactoprotein secretion throughout the lactation cycle. This study investigated the possible modulation by cAMP-mediated mechanisms, of cellular transit of newly-synthesised caseins and their basal secretion in explants of mammary tissue from lactating rats and rabbits. Enhancement of the rate of secretion of newly-synthesised caseins occurs when mammary explants are challenged in vitro with agents that activate protein kinase A (PKA). Inhibition of PKA slows casein secretion. The PKA-sensitive step(s) in casein secretion is early in the exocytosis pathway but inhibition of PKA does not impair casein maturation. Ultrastructural, immunochemical and biochemical methods locate PKA on membranes of vesicles situated in the Golgi region. Exposure of tissue to a cell-permeant PKA inhibitor results in morphological modification of these vesicular structures. We conclude that PKA mediates tonic positive regulation of the basal secretory pathway for lactoproteins in the mammary epithelial cell.
Clegg
R A
RA
Hannah Research Institute, Ayr, Scotland, UK. CLEGGR@main.hri.sari.ac.uk
Gardner
R A
RA
Lavialle
F
F
Boisgard
R
R
Ollivier-Bousquet
M
M
D000818:Animals; D015153:Blotting, Western; D002364:Caseins / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D066298:In Vitro Techniques; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D002364:Caseins; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; C518603:protein kinase inhibitor peptide (5-24); D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D004837:Epinephrine