Role of Gi-proteins in norepinephrine-mediated vasoconstriction in rat tail artery smooth muscle

Petitcolin, Marie-Anne; Spitzbarth-Régrigny, Esther; Bueb, Jean-Luc; Capdeville-Atkinson, Christine; Tschirhart, Eric

doi:10.1016/s0006-2952(01)00589-5

Cited by 11 publications

(2 citation statements)

References 22 publications

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“…These receptors are classically coupled to Gq/11 proteins (but are also reported to be coupled to Gi proteins) and they are activated by catecholamines (adrenaline, noradrenaline, dopamine) [ 17 , 18 ]. The ligand binding on the receptor induces the dissociation of the Gq/11 protein which activates the phospholipase C (PLC).…”

Section: Alpha 1 -Adrenergic Receptor Antagonismentioning

confidence: 99%

Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

Florent

Poulain

N’Diaye

2020

IJMS

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Failure of conventional treatments is often observed in cancer management and this requires the development of alternative therapeutic strategies. However, new drug development is known to be a high-failure process because of the possibility of a lower efficacy than expected for the drug or appearance of non-manageable side effects. Another way to find alternative therapeutic drugs consists in identifying new applications for drugs already approved for a particular disease: a concept named “drug repurposing”. In this context, several studies demonstrated the potential anti-tumour activity exerted by α1-adrenergic receptor antagonists and notably renewed interest for naftopidil as an anti-cancer drug. Naftopidil is used for benign prostatic hyperplasia management in Japan and a retrospective study brought out a reduced incidence of prostate cancer in patients that had been prescribed this drug. Further studies showed that naftopidil exerted anti-proliferative and cytotoxic effects on prostate cancer as well as several other cancer types in vitro, as well as ex vivo and in vivo. Moreover, naftopidil was demonstrated to modulate the expression of Bcl-2 family pro-apoptotic members which could be used to sensitise cancer cells to targeting therapies and to overcome resistance of cancer cells to apoptosis. For most of these anti-cancer effects, the molecular pathway is either not fully deciphered or shown to involve α1-adrenergic receptor-independent pathway, suggesting off target transduction signals. In order to improve its efficacy, naftopidil analogues were designed and shown to be effective in several studies. Thereby, naftopidil appears to display anti-cancer properties on different cancer types and could be considered as a candidate for drug repurposing although its anti-cancerous activities need to be studied more deeply in prospective randomized clinical trials.

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Section: Alpha 1 -Adrenergic Receptor Antagonismentioning

confidence: 99%

Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

Florent

Poulain

N’Diaye

2020

IJMS

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“…This decreases the sensitivity for contraction-inducing agonists. [41][42][43] Consequently, maintaining blood pressure is impaired, possibly leading to the observed hypotonic responses, especially in the presence of vasodilating agents such as histamine. This PT-induced inability of the vascular system to respond to histamine-induced vasodilation, that leads to decreased blood pressure and mortality in mice is very likely the underlying mechanism of the HIST.…”

Section: Adp-ribosylation Of G Proteins Is a Common Mechanism Underlymentioning

confidence: 99%

Toward a mechanism-based in vitro safety test for pertussis toxin

Vaessen¹,

Bruysters

Vandebriel

et al. 2014

Human Vaccines & Immunotherapeutics

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Pertussis vaccines are routinely administered to infants to protect them from whooping cough. Still, an adequate safety test for pertussis toxin (PT), one of the main antigens in these vaccines, is not available. The histamine sensitization test is currently the only assay accepted by regulatory authorities to test for the absence of active PT in vaccines. This is however, a lethal animal test with poor reproducibility. In addition, it is not clear whether the assumed underlying mechanism, i.e., ADP-ribosylation of G proteins, is the only effect that should be considered in safety evaluation of PT. The in vitro safety test for PT that we developed is based on the clinical effects of PT in humans. For this, human cell lines were chosen based on the cell types involved in the clinical effects of PT. These cell lines were exposed to PT and analyzed by microarray. In this review, we discuss the clinical effects of PT and the mechanisms that underlie them. The approach taken may provide as an example for other situations in which an in vitro assay based on clinical effects in humans is required.

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Signal transduction and regulation: Are all α1-adrenergic receptor subtypes created equal?

Hein

Michel

2007

Biochemical Pharmacology

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Role of Gi-proteins in norepinephrine-mediated vasoconstriction in rat tail artery smooth muscle

Cited by 11 publications

References 22 publications

Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

Drug Repositioning of the α1-Adrenergic Receptor Antagonist Naftopidil: A Potential New Anti-Cancer Drug?

Toward a mechanism-based in vitro safety test for pertussis toxin

Signal transduction and regulation: Are all α1-adrenergic receptor subtypes created equal?

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