PDE4 inhibitors induce emesis in ferrets via a noradrenergic pathway

Robichaud, Annette; Savoie, Chantal; Stamatiou, Panagiota B.; Tattersall, F.D.; Chen, Chan

doi:10.1016/s0028-3908(00)00142-8

Cited by 119 publications

(134 citation statements)

References 15 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…This result demonstrates that clinical dosage levels of cisplatin elicit increases in salivary amylase in rats. It is well known that cisplatin (12,17,18) and rolipram (19 -24) are strong emetic agents in humans, dogs, and ferrets; and the latency to the first vomiting is 1 -1.5 h after cisplatin administration to humans, dogs, monkeys and ferrets (12, 13, 25 -27) and within 0.5 h after rolipram administration to humans, ferrets, and dogs (21,22,28). In this study, significant increases in amylase activity were observed at 1.5 h after the administration of cisplatin and at 0.5 h after the administration of rolipram.…”

Section: Discussionmentioning

confidence: 99%

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

et al. 2010

View full text Add to dashboard Cite

Abstract. We investigated the effects of various emetic agents: cisplatin, apomorphine, lithium chloride (LiCl), rolipram, sibutramine, and the β 3 -adrenoceptor (AR) agonist CL316243 on salivary amylase secretion in rats. We also determined the inhibitory effect of granisetron, a 5-HT 3 -receptor antagonist, on cisplatin-induced increased salivary amylase activity and the inhibitory effect of bilateral abdominal vagotomy on increases in salivary amylase activity induced by cisplatin and LiCl. Granisetron was administered 15 min before and 1 h after cisplatin administration. Cisplatin (10 -15 mg/kg, i.v.) increased salivary amylase activity dose-dependently and induced an acute increase from 1.5 h post-treatment with 15 mg/kg. Apomorphine (1 -3 mg/kg, s.c.), LiCl (120 mg/kg, i.p.), rolipram (3 -10 mg/kg, p.o.), and sibutramine (10 mg/kg, p.o.) induced significant increases in salivary amylase secretion. On the other hand, CL316243 did not stimulate salivary amylase secretion. The increased amylase activity induced by cisplatin (15 mg/kg, i.v.) was inhibited significantly by granisetron (1 or 3 mg/kg × 2, i.v.) or tended to be inhibited by bilateral abdominal vagotomy, whereas an increase in amylase activity produced by LiCl was not inhibited by abdominal visceral nerve section. These results suggest that salivary amylase activity is useful as a marker for emesis in rats, a species that does not exhibit vomiting.

show abstract

Section: Discussionmentioning

confidence: 99%

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Extensive research has been performed on PDEs in T lymphocytes to exploit their potential for treating clinical conditions such as: inflammatory disorders, chronic obstructive pulmonary diseases, cancer, multiple sclerosis, and other neurological disorders (8,15). However, because PDEs are ubiquitous, general inhibitors of PDE often have severe side effects (33,34). To combat such limitations, isoform-specific inhibitors have been explored as potential therapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

A-Kinase Anchoring Proteins Interact with Phosphodiesterases in T Lymphocyte Cell Lines

Asirvatham

Galligan

Schillace

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

The cAMP protein kinase A (PKA) pathway in T cells conveys an inhibitory signal to suppress inflammation. This study was performed to understand the mechanisms involved in cAMP-mediated signaling in T lymphocytes. A-kinase anchoring proteins (AKAPs) bind and target PKA to various subcellular locations. AKAPs also bind other signaling molecules such as cyclic nucleotide phosphodiesterases (PDEs) that hydrolyze cAMP in the cell. PDE4 and PDE7 have important roles in T cell activation. Based on this information, we hypothesized that AKAPs associate with PDEs in T lymphocytes. Immunoprecipitation of Jurkat cell lysates with Abs against both the regulatory subunit of PKA (RIIα) and specific AKAPs resulted in increased PDE activity associated with RIIα and AKAP95, AKAP149, and myeloid translocation gene (MTG) compared with control (IgG). Immunoprecipitation and pull-down analyses demonstrate that PDE4A binds to AKAP149, AKAP95, and MTG, but not AKAP79, whereas PDE7A was found to bind only MTG. Further analysis of MTG/PDE association illustrated that PDE4A and PDE7A bind residues 1–344 of MTG16b. Confocal analysis of HuT 78 cells stained with anti-PDE7A showed overlapping staining patterns with the Golgi marker GM130, suggesting that PDE7A is located in the Golgi. The staining pattern of PDE7A also showed similarity to the staining pattern of MTG, supporting the immunoprecipitation data and suggesting that MTG may interact with PDE7A in the Golgi. In summary, these data suggest that AKAPs interact with both PKA and PDE in T lymphocytes and thus are a key component of the signaling complex regulating T cell activation.

show abstract

“…29 The mechanism for the antiemetic effect is as yet unknown: a reduction of selective brain adrenergic stimulation or an intrinsic structure-related effect on ventral brainstem imidazoline receptors have been hypothesized. 27,29 There is no report of its use and effect in HG. As far as we know, this is the first study to report on the effect of clonidine in HG.…”

Section: Discussionmentioning

confidence: 99%

A novel approach to hyperemesis gravidarum: evaluation by a visual analogue scale score and treatment with transdermal clonidine

Maina

Todros

2011

Obstet Med

View full text Add to dashboard Cite

SummaryObjective: A preliminary report on the symptomatic effect of clonidine in severe hyperemesis gravidarum (HG). Design: Observational. Settting: Hospital based: Ospedale Sant'Anna, Torino, Italy. Population: Twelve pregnant women, 8 -16 weeks, affected by severe, refractory HG. Methods: Assessment by two clinical score indexes: Pregnancy Unique Quantification of Emesis (PUQE) score and a Visual Analogue Scale (VAS) 5-item questionnaire, filled out daily, to detect subjective improvement or worsening of symptoms. Main outcome measures: PUQE score and VAS score before and after transdermal clonidine treatment. Results: We found substantial improvement of symptoms and severity score indexes after four and 14 days. The comparison of pretreatment and post-treatment scores shows a significant statistical difference P , 0.0001. Conclusion: Transdermal clonidine may be considered as a treatment for resistant severe HG.

show abstract

PDE4 inhibitors induce emesis in ferrets via a noradrenergic pathway

Cited by 119 publications

References 15 publications

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

A-Kinase Anchoring Proteins Interact with Phosphodiesterases in T Lymphocyte Cell Lines

A novel approach to hyperemesis gravidarum: evaluation by a visual analogue scale score and treatment with transdermal clonidine

Contact Info

Product

Resources

About