Type IV phosphodiesterase activity specifically regulates cAMP-stimulated casein secretion in the rat mammary gland.
This study investigates the regulation of cAMP-stimulated casein secretion in rat mammary explants by cAMP phosphodiesterase (cAMP-PDE) activity. cAMP-PDE activity of the lactating rat mammary gland is shown to be provided by three families, types II, III and IV. In mammary explants, general inhibition of the cAMP-PDE activity significantly increased the rate of cAMP-stimulated casein secretion. This effect could be mimicked using the type-IV specific inhibitor rolipram but not by the specific, or combined, inhibition of the type II and type III activity. Only type IV activity significantly affected intracellular accumulation of cAMP whereas all three cAMP-PDE activities were shown to influence the PKA activation ratio in cells. RtPCR analysis showed that the mammary gland apparently expresses just three type IV isozymes, RNPDE4A5, RNPDE4A8 and RNPDE4D3. A specific role for type IV cAMP-PDE activity in the regulation of casein secretion is suggested and possible mechanisms for the effects of PDEIV activity discussed.
Pooley
Linda
L
Hannah Research Institute, Hannah Research Park, Ayr, KA6 5HL, Scotland, UK. pooleyl@hri.sari.ac.uk
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002364:Caseins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology
D002364:Caseins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D000242:Cyclic AMP; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram