Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury

Background Spinal nitric oxide (NO) is important for the analgesic actions of morphine and cholinergic agents. Its role in the analgesic effect of delta-opioid receptor agonists is not known. In the present study, the authors determined the role of spinal endogenous NO in the antinociceptive effect of intrathecal [D-Pen2, D-Pen5 ]-enkephalin (DPDPE), a delta-opioid receptor agonist, in normal rats and a rat model of diabetic neuropathic pain. Methods Rats were rendered diabetic with streptozotocin (50 mg/kg, intraperitoneal). Intrathecal catheters were implanted in age-matched normal and diabetic rats. Nociceptive thresholds were determined by application of a noxious pressure stimulus to the hind paw. The dose-dependent effect of intrathecal DPDPE was first determined. The role of spinal NO in the analgesic effect of intrathecal DPDPE was then examined through intrathecal treatments with NO synthase inhibitors (NMMA and TRIM) and a specific NO scavenger (carboxy-PTIO). Results The diabetic rats developed a sustained mechanical hyperalgesia within 3 weeks after streptozotocin injection. Intrathecal DPDPE, 2-20 micro g, dose-dependently increased the withdrawal threshold in response to the noxious pressure in normal and diabetic rats. However, the ED(50) of DPDPE in diabetic rats was about twofold higher than that in normal rats. Intrathecal pretreatment with NMMA, TRIM, or carboxy-PTIO diminished the analgesic effect of DPDPE in both normal and diabetic rats. Furthermore, the inhibitory effect of NMMA on the action of intrathecal DPDPE was reversed by intrathecal l-arginine but not d-arginine. Conclusions Intrathecal DPDPE produces an antinociceptive effect in normal rats and a rat model of diabetic neuropathic pain. Spinal endogenous NO contributes importantly to the analgesic action of intrathecal DPDPE in both normal and diabetic neuropathic pain conditions.

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Role of Oleanolic acid in maintaining BBB integrity by targeting p38MAPK/VEGF/Src signaling pathway in rat model of subarachnoid hemorrhage

European Journal of Pharmacology ◽

10.1016/j.ejphar.2018.09.018 ◽

2018 ◽

Vol 839 ◽

pp. 12-20 ◽

Cited By ~ 13

Author(s):

Yu-Wei Han ◽

Xiu-Juan Liu ◽

Ying Zhao ◽

Xiao-Ming Li

Keyword(s):

Subarachnoid Hemorrhage ◽

Signaling Pathway ◽

Oleanolic Acid ◽

Rat Model ◽

Src Signaling

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AT1-Receptorblocker Versus Angiotensin Converting Enzyme Inhibitor in Acute Myocardial Infarction? Role of Dosage and Bradykinin on Remodeling, Hemodynamics and Mortality in the Rat Model

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)85064-4 ◽

1998 ◽

Vol 31 (2) ◽

pp. 311A

Author(s):

P Gaudron

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Angiotensin Converting Enzyme ◽

Angiotensin Converting Enzyme Inhibitor ◽

Rat Model ◽

Enzyme Inhibitor ◽

Converting Enzyme ◽

Converting Enzyme Inhibitor

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Analgesic Effect of Ketoprofen Is Mainly Associated to its R-Enantiomer: Role of Cytokine Modulation

Analgesia ◽

10.3727/107156999819565829 ◽

1999 ◽

Vol 4 (2) ◽

pp. 181-186 ◽

Cited By ~ 1

Author(s):

Riccardo Bertini ◽

Gianfranco Caselli

Keyword(s):

Analgesic Effect ◽

Cytokine Modulation

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Role of pomegranate extract in restoring endometrial androgen receptor expression, proliferation, and pinopodes in a rat model of polycystic ovary syndrome

Morphologie ◽

10.1016/j.morpho.2021.04.004 ◽

2021 ◽

Author(s):

M.A.A. Ibrahim ◽

M.T. Sadek ◽

H.E.M. Sharaf Eldin

Keyword(s):

Androgen Receptor ◽

Polycystic Ovary Syndrome ◽

Rat Model ◽

Polycystic Ovary ◽

Receptor Expression ◽

Androgen Receptor Expression ◽

Ovary Syndrome

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The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes

Medicina ◽

10.3390/medicina56120633 ◽

2020 ◽

Vol 56 (12) ◽

pp. 633

Author(s):

Lore De Kock ◽

Kathleen Freson

Keyword(s):

Platelet Activation ◽

Knockout Mice ◽

Missense Variant ◽

Surface Receptors ◽

Src Signaling ◽

Normal Platelet ◽

Fibrinogen Binding ◽

Cellular Environment ◽

Proplatelet Formation

Proto-oncogene tyrosine-protein kinase SRC (SRC), as other members of the SRC family kinases (SFK), plays an important role in regulating signal transduction by different cell surface receptors after changes in the cellular environment. Here, we reviewed the role of SRC in platelets and megakaryocytes (MK). In platelets, inactive closed SRC is coupled to the β subunit of integrin αIIbβ3 while upon fibrinogen binding during platelet activation, αIIbβ3-mediated outside-in signaling is initiated by activation of SRC. Active open SRC now further stimulates many downstream effectors via tyrosine phosphorylation of enzymes, adaptors, and especially cytoskeletal components. Functional platelet studies using SRC knockout mice or broad spectrum SFK inhibitors pointed out that SRC mediates their spreading on fibrinogen. On the other hand, an activating pathological SRC missense variant E527K in humans that causes bleeding inhibits collagen-induced platelet activation while stimulating platelet spreading. The role of SRC in megakaryopoiesis is much less studied. SRC knockout mice have a normal platelet count though studies with SFK inhibitors point out that SRC could interfere with MK polyploidization and proplatelet formation but these inhibitors are not specific. Patients with the SRC E527K variant have thrombocytopenia due to hyperactive SRC that inhibits proplatelet formation after increased spreading of MK on fibrinogen and enhanced formation of podosomes. Studies in humans have contributed significantly to our understanding of SRC signaling in platelets and MK.

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