title: Functional plasticity of cyclic AMP hydrolysis in rat adenohypophysial corticotroph cells.
abstract: Characterisation of cyclic nucleotide-hydrolysing phosphodiesterases (PDEs) in recombinant systems has highlighted regulatory properties indicative of distinct physiological roles for these enzymes. The present study investigated the role of PDEs in the adenosine 3'5'-monophosphate (cAMP) response to the hypothalamic neuropeptides corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) in acutely dispersed rat adenohypophysial cells. Ca(2+)-activated PDE (PDE1) and Ca(2+)-independent, rolipram-sensitive PDE (PDE4) accounted for close to 90% of cAMP-hydrolysing activity in the adenohypophysis. Messenger RNA transcripts of PDE1 (isotypes 1A and 1C) and PDE4 (isotypes B and D3) were detected by RT-PCR. The PDE blockers rolipram and IBMX enhanced cAMP accumulation induced by CRF or CRF and AVP. Vinpocetine, an inhibitor of low K(m) PDE1 isotypes, did not alter the response to CRF but enhanced the effect of the combined CRF/AVP stimulus. Thus, PDE4s terminate the cAMP response to moderate stimulation, while low-affinity PDE1 becomes important when the concentrations of CRF and AVP are characteristic of exposure to intensive stress.
authors.affiliation: Department of Neuroscience, University of Edinburgh, 1 George Square, EH8 9JZ, Edinburgh, UK.
authors.forename: Kok Long
authors.initials: KL
authors.lastname: Ang
authors.forename: Ferenc A
authors.initials: FA
authors.lastname: Antoni
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006868:Hydrolysis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000494:pharmacology
chemical_list: D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram; D015056:1-Methyl-3-isobutylxanthine