Modulation of Central Control of Hypotensive Effects by Neuropeptide Y is Mediated through RSK Induced Activation of Endothelial Nitric Oxide Synthase.
Summary of "Modulation of Central Control of Hypotensive Effects by Neuropeptide Y is Mediated through RSK Induced Activation of Endothelial Nitric Oxide Synthase."
Background and purpose: Neuropeptide Y (NPY) is a 36-amino-acid polypeptide found abundantly in the central and peripheral nervous system. It has been demonstrated that NPY exerts a potent depressor effect via the activation of both NPYY1 and NPYY2 receptors in the nucleus tractus solitarii (NTS) of rats. However, the precise mechanisms involved in NPY-mediated activity remained unclear. Experimental approach: Microinjection of NPY into the NTS of Wistar-Kyoto rats in the absence or presence of a selective non-peptide antagonist of the NPYY1 receptor, PKC inhibitor, PI3 kinase inhibitor, nitric oxide synthase (NOS) inhibitor, endothelial NOS (eNOS)-selective inhibitor, neuronal NOS (nNOS)-specific inhibitor or MAP kinase inhibitor, was used to determine the underlying mechanism of NPY-induced depressor effect in the NTS. Key results: Unilateral microinjection of exogenous NPY (4.65 pmol/60 nL) into the NTS of urethane-anesthetized Wistar-Kyoto rats resulted in a prominent decrease in blood pressure and heart rate. Microinjection of NPYY1 receptor antagonist BIBP3226 or Gi/Go-protein inhibitor pertussis toxin into the NTS attenuated NPY-induced hypotensive effects. An NPYY1 agonist significantly increased the expression of extracellular signal-regulated kinase (ERK)1/2, ribosomal protein S6 kinase (RSK) and the phosphorylation of eNOS. RSK was also found to bind directly to eNOS and induced its phosphorylation at Ser1177. However, pretreatment with an eNOS inhibitor, but not a nNOS inhibitor, attenuated NPY-induced depressor and bradycardic effects in the NTS. Conclusions and implications: Collectively, these results suggested that NPY induced depressor effects are mediated by activating NPYY1 receptor-PKC-ERK-RSK-eNOS and Ca(2+) -eNOS signaling pathways which are involved in the regulation of blood pressure in the NTS. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Radiation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Institute of Clinical Medicine, National Che
This article was published in the following journal.
Name: British journal of pharmacology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22708658
- DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.02077.x
Medical and Biotech [MESH] Definitions
Alkaloids with powerful hypotensive effects isolated from American or European Hellebore (Veratrum viride Ait. Liliaceae and Veratrum album L. Liliaceae). They increase cholinergic and decrease adrenergic tone with appropriate side effects and at higher doses depress respiration and produce cardiac arrhythmias; only the ester alkaloids have been used as hypotensive agents in specific instances. They have been generally replaced by drugs with fewer adverse effects.
A sympathomimetic agent with mainly indirect effects on adrenergic receptors. It is used to maintain blood pressure in hypotensive states, for example, following spinal anesthesia. Although the central stimulant effects of mephentermine are much less than those of amphetamine, its use may lead to amphetamine-type dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1248)
A hypotensive agent with some anti-arrhythmic effects.
Laser Therapy, Low-level
Treatment using irradiation with LASER light of low power intensity so that the effects are not due to heat, as in LASER THERAPY. These non-thermal effects are thought to be mediated by a photochemical reaction that alters CELL MEMBRANE PERMEABILITY, leading to increased mRNA synthesis and CELL PROLIFERATION. Low-level laser therapy has been used for a wide variety of conditions, but most frequently for wound healing and pain control.
Pituitary Adenylate Cyclase-activating Polypeptide
A multi-function neuropeptide that acts throughout the body by elevating intracellular cyclic AMP level via its interaction with PACAP RECEPTORS. Although first isolated from hypothalamic extracts and named for its action on the pituitary, it is widely distributed in the central and peripheral nervous systems. PACAP is important in the control of endocrine and homeostatic processes, such as secretion of pituitary and gut hormones and food intake.
Accumulating evidence has contributed to a novel view in bone biology: bone remodeling, specifically osteoblast differentiation, is under the tight control of the central and peripheral nervous system...
Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered...
Glucagon-like peptide 1(GLP-1) is both an incretin released postprandially from the gut and a neuropeptide produced by select brainstem neurons. Its principal role is in the control of metabolic and c...
The new pathway nitrate-nitrite-nitric oxide (NO) has emerged as a physiological alternative to the classical enzymatic pathway for NO formation from l-arginine. Nitrate is converted to nitrite by com...
The purpose of the study is to test whether hypotensive episodes during dialysis - caused by withdrawal of fluid drom the circulation - can be predicted by means of two harmless monitoring...
Visceral hypersensitivity as evidence of central sensory sensitization is evident in many patients with functional disorders such as functional dyspepsia (FD) and irritable bowel syndrome...
Background. Patients with chronic low back pain display hyperexcitability of the central nervous system (central hypersensitivity). Such hypersensitivity may occur in the acute phase and r...
For the ESRD patients undergoing hemodialysis treatment, specifically, reflex mediated calf muscle pump stimulation has the potential to significantly reduce the number and magnitude of hy...
A double-masked, randomized, vehicle-controlled, dose-response study assessing the safety and ocular hypotensive efficacy of AR-102 in subjects with elevated intraocular pressure. The Null...