The DOI matches its Crossref record; 42 of the 44 references it cites were found in a registry or an index.
Deletion of phosphodiesterase 4D in mice shortens α2-adrenoceptor–mediated anesthesia, a behavioral correlate of emesis
Open accessAbstract
A combination of pharmacological and genetic approaches was used to determine the role of type 4 cAMP-specific cyclic nucleotide phosphodiesterase 4 (PDE4) in reversing alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis in non-vomiting species. Among the family-specific PDE inhibitors, PDE4 inhibitors reduced the duration of xylazine/ketamine-induced anesthesia in mice, with no effect on pentobarbital-induced anesthesia. The rank order of the PDE4 inhibitors tested was 6-(4-pyridylmethyl)-8-(3-nitrophenyl)quinoline (PMNPQ) > (R)-rolipram > (S)-rolipram >> (R)-N-[4-[1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]phenyl]N'-ethylurea (CT-2450). The specific roles of PDE4B and PDE4D in this model were studied using mice deficient in either subtype. PDE4D-deficient mice, but not PDE4B-deficient mice, had a shorter sleeping time than their wild-type littermates under xylazine/ketamine-induced anesthesia, but not under that induced with pentobarbital. Concomitantly, rolipram-sensitive PDE activity in the brain stem was decreased only in PDE4D-deficient mice compared with their wild-type littermates. While PMNPQ significantly reduced the xylazine/ketamine-induced anesthesia period in wild-type mice and in PDE4B-null mice, it had no effect in PDE4D-deficient mice. These findings strongly support the hypothesis that inhibition of PDE4D is pivotal to the anesthesia-reversing effect of PMNPQ and is likely responsible for emesis induced by PDE4 inhibitors.
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BackgroundMethodA novel phosphodiesterase inhibitor for the treatment of chronic liver injury and metabolic diseases
Staller, D. W., Panigrahi, S. S., Jayasinghe, Y. P., Dong, Y., Mahto, S., Kumar, V., Ronning, D. R., & Mahato, R. I. (2024) · Hepatology · doi:10.1097/hep.0000000000000999 · Cited by 10
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BackgroundGastrointestinale Beschwerden unter Apremilast
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“PDE4 wird überwiegend in Monozyten, T-Zellen und Neutrophilen exprimiert, findet sich aber auch in einigen ortsständigen Zelltypen wie in Keratinozyten und anderen Epithelzellen, in Endothelzellen, glatten Muskelzellen sowie im Gehirn [4, 5].”
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Metadata
- Authors
- Robichaud, A., Stamatiou, P. B., Jin, S.-L. C., Lachance, N., MacDonald, D., Laliberté, F., Liu, S., Huang, Z., Conti, M., & Chan, C.-C.
- Affiliations
- Merck Canada Inc. (Canada) (CA)
- Stanford Medicine (US)
- Corresponding author
- Robichaud, Annette
- Venue
- Journal of Clinical Investigation
- Published
- 2002-10-01
- Volume
- 110
- Issue
- 7
- Pages
- 1045-1052
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC151147
- OpenAlex
- W2170451911
- Cited by
- 267
- References
- 44
- Citations by year
- 2026: 4 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 7 · 2017: 14 · 2016: 10 · 2015: 11 · 2014: 22 · 2013: 11 · 2012: 19
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD020788, HD20788)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
- Keywords
- PDE4D, PDE4B, phosphodiesterase-4 inhibitors, vomiting, ketamine-xylazine anesthesia, rolipram, sleep duration, cAMP signaling
- MeSH terms
- Anesthesia, Animals, Male, Mice, Inbred C57BL, Pentobarbital, Phosphodiesterase Inhibitors, Time Factors, Vomiting, 3',5'-Cyclic-AMP Phosphodiesterases, Receptors, Adrenergic, alpha-2, Mice, Cyclic Nucleotide Phosphodiesterases, Type 4
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