Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to determine if PACAP synergistically interacts with vasopressin (VP) and protein kinase C (PKC) to enhance cyclic AMP formation and adrenocorticotrophic hormone (ACTH) secretion, the effects of PACAP, either alone or together with VP and the phorbol ester phorbol 12-myristate 13-acetate (PMA) were examined in primary cultures of rat anterior pituitary cells. VP failed to potentiate the stimulatory effect of PACAP on cyclic AMP formation, while it dramatically enhanced the effect of corticotropin-releasing factor (CRF). However, activation of PKC upon exposure of cells to PMA amplified cyclic AMP production induced by both peptides, though in the case of PACAP, contrary to that of CRF, potentiation was markedly dependent on the blockade of phosphodiesterase (PDE) activity, for it was undetectable in the absence of the inhibitor Rolipram. Depletion of PKC by long-term treatment of pituitary cells with PMA abolished the synergistic influence of PMA. There was no significant effect of PACAP, either alone or together with PMA, on ACTH secretion, while PMA enhanced peptide secretion elicited by CRF. The data show that in anterior pituitary cells cyclic AMP accumulation induced by PACAP and CRF was differentially modulated by PKC and PDE activities and that the potentiation of PACAP-stimulated cyclic AMP accumulation by PMA was not reflected by parallel increment of ACTH secretion.
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PMID:Vasopressin, unlike phorbol ester, fails to synergistically interact with pituitary adenylate cyclase activating polypeptide (PACAP) in stimulating cyclic AMP formation and ACTH secretion in cultured anterior pituitary cells. 839 88

To evaluate the roles of cAMP degradation on hormonal actions in the kidney, we examined the segmental distribution and activities of cAMP-phosphodiesterase (PDE), a key enzyme for cAMP hydrolysis, in dissected segments of the rat nephron and characterized the isozyme compositions with subtype-specific inhibitors. Summary of the nephron distribution of PDE activities showed that cAMP-PDE activities were detected in all nephron segments and the distal convoluted tubules (DCTs) had the highest activity. Both in proximal convoluted tubules (PCTs) and medullary collecting ducts (MCDs), more than 80% of the total cAMP-PDE activities were inhibited by a nonspecific PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX). In PCTs, rolipram (type-IV PDE inhibitor) was an equally potent inhibitor of IBMX, while 8-methoxymethyl-IBMX (MM-IBMX, type-I PDE inhibitor) and cilostamide (type-III PDE inhibitor) inhibited cAMP-PDE by 35 and 57%, respectively. In MCDs, inhibition by rolipram (40%) was less than that by MM-IBMX (70%) or cilostamide (66%). Rolipram potentiated the parathyroid hormone (PTH)-induced cAMP content in PCTs most effectively. Rolipram and MM-IBMX increased the vasopressin (AVP)-stimulated cAMP content equally in MCDs. Cilostamide had no effect on the cAMP content stimulated by PTH or AVP in PCTs and MCDs. These results indicate that PDE activities were unevenly distributed along the rat nephron and cAMP-PDE was composed of at least three isoforms, namely type I, III and IV in PCTs and MCDs. Among these, type-IV PDE was responsible for hydrolysis of cAMP in PCTs, and type-I and IV PDE were responsible for that in MCDs.
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PMID:Localization of low-KM cAMP phosphodiesterase in rat nephron segments. 941 46

Neonates cannot concentrate their urine to the same degree as adults. One of the key factors in concentrating the urine is the renal collecting duct osmotic water permeability (Pf) response to antidiuretic hormone (ADH). Neonatal cortical collecting ducts have a blunted Pf response to ADH compared with adult tubules (Pf: 119.0 +/- 12.5 vs. 260.1 +/- 29.5 microm/s, P < 0.05). We found that the phosphodiesterase activity in the neonatal collecting ducts was higher than that in the adult collecting ducts (3,970 +/- 510 vs. 2,440 +/- 220 cpm.microg tubular protein-1.20 min-1, P < 0.05). After pretreatment of in vitro microperfused tubules with the nonspecific phosphodiesterase inhibitor IBMX (10-6 M in the bath), the Pf response to ADH in neonatal collecting ducts was 271.4 +/- 51.7 microm/s, which was identical to that of the adult collecting duct [315.3 +/- 31.3 microm/s, P = not significant (NS)]. Rolipram, a specific type IV phosphodiesterase inhibitor, lowered the elevated phosphodiesterase activity in the neonatal tubules to that in the adult tubules (2,460 +/- 210 vs. 2,160 +/- 230 cpm.microg tubular protein-1.20 min-1, P = NS). Neonatal tubules pretreated with rolipram (10-5 M) in the bath also had a Pf response to ADH that was comparable to that of the adult tubules (258.2 +/- 17.0 vs. 271.4 +/- 32.6 microm/s, P = NS). Thus the elevated phosphodiesterase activity in the neonatal tubules appears to be due to an increase in type IV phosphodiesterase activity. Hence, one of the key factors in the decreased ability of neonates to concentrate their urine is overactivity of phosphodiesterase in the cortical collecting duct that blunts the neonatal collecting duct Pf response to ADH.
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PMID:Antidiuretic hormone resistance in the neonatal cortical collecting tubule is mediated in part by elevated phosphodiesterase activity. 1464 47