Rolipram

cAMP pathway activator; Inhibits type 4 cyclic nucleotide phosphodiesterases (PDE4)

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cAMP pathway activator; Inhibits type 4 cyclic nucleotide phosphodiesterases (PDE4)
From: 33 USD

Overview

Rolipram is a cell-permeable, selective inhibitor of Type 4 cyclic nucleotide phosphodiesterases (PDE4), which mediate cyclic AMP (cAMP) degradation. Rolipram preferably inhibits PDE4 isoform A (IC₅₀ = 3 nM) over other isoforms such as B and D (IC₅₀ = 130 and 240 nM respectively; MacKenzie & Houslay). It inhibits interferon (IFN)-γ stimulated phosphorylation of p38 mitogen-activated protein (MAP) kinase through PDE4B and/or PDE4D isoform inhibition (MacKenzie & Houslay).

DIFFERENTIATION
· Enhances osteoblastic differentiation of mouse mesenchymal stem cells (MSCs) induced by BMP-2 (Munisso et al.)
· Induces neural differentiation of human bone marrow-derived MSCs (Alexanian et al.)

REPROGRAMMING
· Induces reprogramming of adult human dermal fibroblasts (AHDFs) into induced neuronal stem cells, in combination with A83-01, CHIR99021, sodium butyrate, LPA, SP600125, and exogenous OCT4 expression (Zhu et al.)

DISEASE MODELING
· Promotes survival of newly formed mouse hippocampal neurons in a mouse model of ischemia (Sasaki et al.)
· Reverses amphetamine-induced reductions in auditory-evoked potentials in a C57BL/6J mouse model of schizophrenia (Maxwell et al.)

IMMUNOLOGY
· Inhibits inflammation by suppressing leukocyte function, inhibiting C5a-stimulated leukotriene C4 (LTC4) synthesis in human eosinophils (Tenor et al.)
· Inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) synthesis in human monocytes (Souness et al.)
Alternative Names:
SB 95952; ZK 62711
CAS Number:
61413-54-5
Chemical Formula:
C₁₆H₂₁NO₃
Molecular Weight:
275.3 g/mol
Purity:
≥ 98%
Pathway:
cAMP
Target:
PDE

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Educational Materials

(4)

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This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Data and Publications

Publications

(8)
Cell research 2014

Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells.

Zhu S et al.

Abstract

Biochimie 2012

Cilomilast enhances osteoblast differentiation of mesenchymal stem cells and bone formation induced by bone morphogenetic protein 2.

Munisso MC et al.

Abstract

A rapid and efficient method to stimulate bone regeneration would be useful in orthopaedic stem cell therapies. Rolipram is an inhibitor of phosphodiesterase 4 (PDE4), which mediates cyclic adenosine monophosphate (cAMP) degradation. Systemic injection of rolipram enhances osteogenesis induced by bone morphogenetic protein 2 (BMP-2) in mice. However, there is little data on the precise mechanism, by which the PDE4 inhibitor regulates osteoblast gene expression. In this study, we investigated the combined ability of BMP-2 and cilomilast, a second-generation PDE4 inhibitor, to enhance the osteoblastic differentiation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity of MSCs treated with PDE4 inhibitor (cilomilast or rolipram), BMP-2, and/or H89 was compared with the ALP activity of MSCs differentiated only by osteogenic medium (OM). Moreover, expression of Runx2, osterix, and osteocalcin was quantified using real-time polymerase chain reaction (RT-PCR). It was found that cilomilast enhances the osteoblastic differentiation of MSCs equally well as rolipram in primary cultured MSCs. Moreover, according to the H89 inhibition experiments, Smad pathway was found to be an important signal transduction pathway in mediating the osteogenic effect of BMP-2, and this effect is intensified by an increase in cAMP levels induced by PDE4 inhibitor.
Neurorehabilitation and neural repair 2011

Transplanted neurally modified bone marrow-derived mesenchymal stem cells promote tissue protection and locomotor recovery in spinal cord injured rats.

Alexanian AR et al.

Abstract

BACKGROUND: Stem cell-based therapy for repair and replacement of lost neural cells is a promising treatment for central nervous system (CNS) diseases. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) can differentiate into neural phenotypes and be isolated and expanded for autotransplantation with no risk of rejection. OBJECTIVE: The authors examined whether transplanted neurally induced human MSCs (NI hMSCs), developed by a new procedure, can survive, differentiate, and promote tissue protection and functional recovery in injured spinal cord (ISC) rats. METHODS: Neural induction was achieved by exposing cells simultaneously to inhibitors of DNA methylation, histone deacetylation, and pharmacological agents that increased cAMP levels. Three groups of adult female Sprague-Dawley rats were injected immediately rostral and caudal to the midline lesion with phosphate-buffered saline, MSCs, or NI hMSCs, 1 week after a spinal cord impact injury at T-8. Functional outcome was measured using the Basso Beattie Bresnahan (BBB) locomotor rating scale and thermal sensitivity test on a weekly basis up to 12 weeks postinjury. Graft integration and anatomy of spinal cord was assessed by stereological, histochemical, and immunohistochemical techniques. RESULTS: The transplanted NI hMSCs survived, differentiated, and significantly improved locomotor recovery of ISC rats. Transplantation also reduced the volume of lesion cavity and white matter loss. CONCLUSION: This method of hMSC modification may provide an alternative source of autologous adult stem cells for CNS repair.
Stroke; a journal of cerebral circulation 2007

The phosphodiesterase inhibitor rolipram promotes survival of newborn hippocampal neurons after ischemia.

Sasaki T et al.

Abstract

BACKGROUND AND PURPOSE: Brain ischemia stimulates neurogenesis. However, newborn neurons show a progressive decrease in number over time. Under normal conditions, the cAMP-cAMP responsive element binding protein (CREB) pathway regulates the survival of newborn neurons. Constitutive activation of CREB after brain ischemia also stimulates hippocampal neurogenesis. Thus, activation of cAMP-CREB signaling may provide a promising strategy for enhancing the survival of newborn neurons. We examined whether treatment of mice with the phosphodiesterase-4 inhibitor rolipram enhances hippocampal neurogenesis after ischemia. METHODS: Both common carotid arteries in mice were occluded for 12 minutes. Bromodeoxyuridine (BrdU) was used to label proliferating cells. Mice were perfused transcardially with 4% paraformaldehyde, and immunohistochemistry was performed. To evaluate the role of CREB in the survival of newborn neurons after ischemia, intrahippocampal injection of a CRE-decoy oligonucleotide was delivered for 1 week. We examined whether the activation of cAMP-CREB signaling by rolipram enhanced the proliferation and survival of newborn neurons. RESULTS: Phospho-CREB immunostaining was markedly upregulated in immature neurons, decreasing to low levels in mature neurons. The number of BrdU-positive cells 30 days after ischemia was significantly less in the CRE-decoy treatment group than in the vehicle group. Rolipram enhanced the proliferation of newborn cells under physiologic conditions but not under ischemic conditions. Rolipram significantly increased the survival of nascent BrdU-positive neurons, accompanied by an enhancement of phospho-CREB staining and decreased newborn cell death after ischemia. CONCLUSIONS: CREB phosphorylation regulates the survival of newborn neurons after ischemia. Chronic pharmacological activation of cAMP-CREB signaling may be therapeutically useful for the enhancement of neurogenesis after ischemia.
Neuroscience 2004

Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications.

Maxwell CR et al.

Abstract

OVERVIEW: All current antipsychotic medications work by binding to Gi-coupled dopamine (DA) D2 receptors. Such medications are thought to affect cellular function primarily by decreasing DA-mediated regulation of intracellular cyclic adenosine monophosphate (cAMP).However, several studies indicate that cAMP signal transduction abnormalities in schizophrenia may not be limited to D2-containing cells. The current study examines the potential of using non-receptor-based agents that modify intracellular signal transduction as potential antipsychotic medications. METHODS: The indirect DA agonist amphetamine has been used to model the auditory sensory processing deficits in schizophrenia. Such pharmacologically induced abnormalities are reversed by current antipsychotic treatments. This study examines the ability of the phosphodiesterase-4 inhibitor, rolipram, to reverse amphetamine-induced abnormalities in auditory-evoked potentials that are characteristic of schizophrenia. RESULTS: Rolipram reverses amphetamine-induced reductions in auditory-evoked potentials. CONCLUSION: This finding could lead to novel approaches to receptor-independent treatments for schizophrenia.
STEMCELL TECHNOLOGIES INC.’S QUALITY MANAGEMENT SYSTEM IS CERTIFIED TO ISO 13485. PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED.