Endothelin B receptor agonist, IRL-1620, provides long-term neuroprotection in cerebral ischemia in rats

Leonard, Mary G.; Briyal, Seema; Gulati, Anil

doi:10.1016/j.brainres.2012.05.005

Cited by 48 publications

(70 citation statements)

References 40 publications

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“…We have demonstrated that activation of ET B receptors with intravenous IRL-1620, a highly selective ET B agonist, results in a significant elevation in cerebral blood flow in normal rats and reduction in neurological deficit and infarct volume of stroked rats (Leonard and Gulati, 2009;Leonard et al, 2011). It was further found that the efficacy of IRL-1620 in a rat model of stroke was completely antagonized by BQ788 indicating involvement of ET B receptors (Leonard et al, 2011(Leonard et al, , 2012.…”

Section: Introductionmentioning

confidence: 93%

“…BQ788 was administered at a dose of 1-mg/kg, i.v., 15 min prior to administration of either vehicle or IRL-1620. The doses of IRL-1620 and BQ788 were based on preliminary studies and previous work conducted in our laboratory (Leonard et al, 2011(Leonard et al, , 2012.…”

Section: Drugs and Experimental Designmentioning

confidence: 99%

“…Water maze testing was performed from day 15 to day 19 when the animals were euthanized. Animals used for Immunofluorescence and Western blot analysis were euthanized on day 15 without being subject to any behavioral testing (Leonard et al, 2011(Leonard et al, , 2012.…”

Section: Drugs and Experimental Designmentioning

confidence: 99%

“…Previous studies in our lab have shown that intravenous (i.v.) administration of IRL-1620 provides neuroprotection and enhances neurovascular recovery following cerebral ischemia (Leonard et al, 2011(Leonard et al, , 2012Leonard and Gulati, 2013). In the current study, we examined the effect of selective stimulation of ET B receptors via intravenous administration of IRL-1620 on memory deficit following Ab injection.…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of endothelin B receptors by IRL-1620 decreases the progression of Alzheimer’s disease

et al. 2015

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Section: Introductionmentioning

confidence: 93%

Section: Drugs and Experimental Designmentioning

confidence: 99%

Section: Drugs and Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stimulation of endothelin B receptors by IRL-1620 decreases the progression of Alzheimer’s disease

et al. 2015

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“…β-Tubulin (1: 2,000; Cell Signaling Technology) or β-actin (1: 10,000; SigmaAldrich) were used as loading controls. The dilutions for all antibodies were determined based on previous studies in our laboratory [19,30,31] using the same antibodies as well as literature provided by the manufacturer. The blots were then visualized with SuperSignal West Pico Chemiluminescent Substrate (Thermo Scientific) using the Kodak Gel Logic 1500 Imaging System (Carestream Health Inc., New Haven, CT, USA).…”

Section: Determination Of Cb 1 and Et B Receptors Vegf And Ngf Exprmentioning

confidence: 99%

Maternal Cannabinoid Use Alters Cannabinoid (CB<sub>1</sub>) and Endothelin (ET<sub>B</sub>) Receptor Expression in the Brains of Dams but Not Their Offspring

Amlani

Hornick²,

Cooper

et al. 2017

Dev Neurosci

Self Cite

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According to the 2015 National Survey on Drug Use and Health, cannabis (marijuana) is the most commonly used recreational drug in the US. Among pregnant women aged 14-55 years, 3.4% were cannabis users. Presently, little is known about the neurodevelopmental effect of cannabis use during pregnancy and/or nursing on neonates. Endothelin (ET) is essential for normal development of the central nervous system (CNS). Decreases in ET_B receptor expression correlate with a decline in nerve growth factor (NGF) and an increase in vascular endothelial growth factor (VEGF) in postnatal brain. Activation of ET_B and cannabinoid 1 (CB₁) receptors each promote neurogenesis and enhance angiogenesis, indicating that both ET and CB systems play a critical role during early CNS development. Hence the purpose of this study was to determine whether maternal CB abuse during pregnancy and lactation alters the expression of ET_B receptors, CB₁ receptors, VEGF, and NGF in the postnatal rat brain. Sixteen pregnant Sprague-Dawley rats were administered either saline or anandamide (AEA) at a dose of 3 mg/kg/day i.p. from gestational day 7 and continued through weaning on postnatal day (PND) 21. Rat pups were subdivided into 4 subgroups and sacrificed on PND 2, 7, 14, and 28. Brain tissue of the pups and dams (sacrificed on PND 21) was analyzed via Western blot for the expression of ET_B receptors, CB₁ receptors, VEGF, and NGF. AEA-exposed dams had significantly fewer live births (p = 0.027), and their pups presented with significantly lower body weights on PND 7 (p = 0.013) and PND 28 (p = 0.018). There was no significant difference noted in ET_B receptor, CB₁ receptor, NGF, or VEGF expression in the pup brains. In all pups, brain ET_B receptor expression decreased and CB₁ receptor expression increased with age. In the AEA-exposed dam brain, however, there was a decrease in ET_B receptor (p = 0.043) and an increase in CB₁ receptor expression (p = 0.033). AEA exposure during pregnancy appears to affect fetal viability and postnatal weight gain in offspring while not altering the expression patterns of ET_B receptors, CB₁ receptors, NGF, or VEGF in the pup brain. The observed trend to an increase in CB₁ receptor expression concurrent with a decrease in ET_B receptor expression in both dams and pups may point to a homeostatic regulation between these 2 systems in CNS development and neuroprotection.

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Endothelin Receptors in Cerebrovascular Diseases

Briyal

Ranjan

Gulati

2022

GPCRs as Therapeutic Targets

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Endothelin B receptor agonist, IRL-1620, provides long-term neuroprotection in cerebral ischemia in rats

Cited by 48 publications

References 40 publications

Stimulation of endothelin B receptors by IRL-1620 decreases the progression of Alzheimer’s disease

Stimulation of endothelin B receptors by IRL-1620 decreases the progression of Alzheimer’s disease

Maternal Cannabinoid Use Alters Cannabinoid (CB<sub>1</sub>) and Endothelin (ET<sub>B</sub>) Receptor Expression in the Brains of Dams but Not Their Offspring

Endothelin Receptors in Cerebrovascular Diseases

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