scholarly journals Effects of Nifedipine on Renal and Cardiovascular Responses to Neuropeptide Y in Anesthetized Rats

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4460
Author(s):  
Angela Bischoff ◽  
Martina Stickan-Verfürth ◽  
Martin C. Michel
Keyword(s):  
Neuropeptide Y ◽  
Cardiovascular Responses ◽  
Receptor Subtypes ◽  
Y1 Receptor ◽  
Mediated Effects ◽  
Anesthetized Rats ◽  
Pre Treatment ◽  
Multiple Receptor ◽  
Ca2 Channels

Neuropeptide Y (NPY) acts via multiple receptor subtypes termed Y1, Y2 and Y5. While Y1 receptor-mediated effects, e.g., in the vasculature, are often sensitive to inhibitors of L-type Ca2+ channels such as nifedipine, little is known about the role of such channels in Y5-mediated effects such as diuresis and natriuresis. Therefore, we explored whether nifedipine affects NPY-induced diuresis and natriuresis. After pre-treatment with nifedipine or vehicle, anesthetized rats received infusions or bolus injections of NPY. Infusion NPY (1 µg/kg/min) increased diuresis and natriuresis, and this was attenuated by intraperitoneal injection of nifedipine (3 µg/kg). Concomitant decreases in heart rate and reductions of renal blood flow were not attenuated by nifedipine. Bolus injections of NPY (0.3, 1, 3, 10 and 30 μg/kg) dose-dependently increased mean arterial pressure and renovascular vascular resistance; only the higher dose of nifedipine (100 μg/kg/min i.v.) moderately inhibited these effects. We conclude that Y5-mediated diuresis and natriuresis are more sensitive to inhibition by nifedipine than Y1-mediated renovascular effects. Whether this reflects a general sensitivity of Y5 receptor-mediated responses or is specific for diuresis and natriuresis remains to be investigated.

scholarly journals The Role of Neuropeptide Y in the Nucleus Accumbens

2021 ◽  
Vol 22 (14) ◽  
pp. 7287
Author(s):  
Masaki Tanaka ◽  
Shunji Yamada ◽  
Yoshihisa Watanabe
Keyword(s):  
Nervous System ◽  
Nucleus Accumbens ◽  
Neuropeptide Y ◽  
Emotional Behavior ◽  
Characteristic Functions ◽  
Receptor Subtypes ◽  
Neuroendocrine Mechanisms ◽  
Fear And Anxiety ◽  
The Brain

Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system.

scholarly journals Role of nitric oxide-containing factors in the ventilatory and cardiovascular responses elicited by hypoxic challenge in isoflurane-anesthetized rats

2014 ◽  
Vol 116 (11) ◽  
pp. 1371-1381 ◽  
Author(s):  
James P. Mendoza ◽  
Rachael J. Passafaro ◽  
Santhosh M. Baby ◽  
Alex P. Young ◽  
James N. Bates ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Cardiovascular Responses ◽  
Vital Role ◽  
Initial Increase ◽  
Ventilatory Responses ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Before And After

Exposure to hypoxia elicits changes in mean arterial blood pressure (MAP), heart rate, and frequency of breathing (fr). The objective of this study was to determine the role of nitric oxide (NO) in the cardiovascular and ventilatory responses elicited by brief exposures to hypoxia in isoflurane-anesthetized rats. The rats were instrumented to record MAP, heart rate, and fr and then exposed to 90 s episodes of hypoxia (10% O2, 90% N2) before and after injection of vehicle, the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME), or the inactive enantiomer d-NAME (both at 50 μmol/kg iv). Each episode of hypoxia elicited a decrease in MAP, bidirectional changes in heart rate (initial increase and then a decrease), and an increase in fr. These responses were similar before and after injection of vehicle or d-NAME. In contrast, the hypoxia-induced decreases in MAP were attenuated after administration of l-NAME. The initial increases in heart rate during hypoxia were amplified whereas the subsequent decreases in heart rate were attenuated in l-NAME-treated rats. Finally, the hypoxia-induced increases in fr were virtually identical before and after administration of l-NAME. These findings suggest that NO factors play a vital role in the expression of the cardiovascular but not the ventilatory responses elicited by brief episodes of hypoxia in isoflurane-anesthetized rats. Based on existing evidence that NO factors play a vital role in carotid body and central responses to hypoxia in conscious rats, our findings raise the novel possibility that isoflurane blunts this NO-dependent signaling.

Abstract 424: Activation of the S1P3 Receptors is Responsible for S1P-mediated RhoA Activation and Cardioprotection

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Bryan S Yung ◽  
Sunny Y Xiang ◽  
Nicole Purcell ◽  
Hugh Rosen ◽  
Jerold Chun ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Cardiovascular Responses ◽  
Neonatal Rat ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
S1p Receptors ◽  
Rhoa Activation ◽  
Therapeutic Benefits

Sphingosine-1-phoshpate (S1P) is a bioactive lysophospholipid, generated and released at sites of tissue injury. S1P signals through a variety of G-protein coupled receptor subtypes and there are three major sub-types, S1P 1 , S1P 2 , and S1P 3 , to mediate cardiovascular responses. S1P 2 and S1P 3 receptors couple to Gα i , Gα 12 , Gα 13 and Gα q and we first examined the contribution of S1P 2 and S1P 3 to cardiac hypertrophy using S1P 2 and S1P 3 knockout (KO) mice and found that there is no difference in hypertrophy induced by pressure-overload. We previously showed that S1P provides cardioprotection against oxidative stress such as ischemia/reperfusion in which RhoA activation and its downstream effector PKD1 play an important role. It has not, however, been determined which S1P receptor subtype is responsible for S1P mediated cardioprotection. We knocked down the three major S1P receptors using siRNA in neonatal rat ventricular myocytes (NRVMs) and assessed RhoA and PKD1 activation induced by S1P. Knockdown of S1P 3 abolished RhoA activation and largely attenuated phosphorylation of PKD1 while knockdown of S1P 1 and S1P 2 did not. Using siRNA or pertussis toxin to inhibit different G-proteins, we further established that S1P regulates RhoA activation through Gα 13 , but not Gα 12 , Gα q , or Gα i . To investigate the role of S1P 3 receptors in the adult heart, hearts were isolated from wild-type or S1P 3 KO adult mice, perfused in the Langendorff mode and subjected to ex vivo ischemia/reperfusion. As previously reported, S1P perfusion significantly reduced infarct size induced by ischemia/reperfusion in WT hearts (by 50%), but this protection was abolished in the S1P 3 KO mouse heart. To further confirm the role of S1P 3 in cardioprotection we perfused WT mouse hearts with an S1P 3 -specific agonist CYM-51736. We observed that CYM-51736 attenuated the infarct size to a similar degree as that observed with S1P. Our findings reveal that activation of the S1P 3 receptor coupling to Gα 13 and subsequent RhoA activation is responsible for cardioprotection against ischemia/reperfusion. Accordingly specific drug targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease without the undesirable effects of global activation of other cardiac S1P receptors.

The role of neuropeptide Y Y1 receptor signalling in fracture healing

2014 ◽  
Author(s):  
Daniela M Sousa ◽  
Michelle M McDonald ◽  
Kathy Mikulec ◽  
Lauren Peacock ◽  
David G Little ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Fracture Healing ◽  
Y1 Receptor ◽  
Receptor Signalling

Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats

1990 ◽  
Vol 259 (3) ◽  
pp. R427-R438
Author(s):  
S. Shapira ◽  
O. M. Adeyemo ◽  
G. Feuerstein
Keyword(s):  
Pressor Response ◽  
Cardiovascular Responses ◽  
Motor Deficits ◽  
Channel Blockers ◽  
Gamma Aminobutyric Acid ◽  
Central Administration ◽  
Arterial Blood ◽  
Behavioral Variables ◽  
Ca2 Channels

omega-Conotoxin (omega-ctx) was used as a probe for studying the putative role of brain L/N-type Ca2+ channels in regulation of autonomic functions. Rats were injected intracerebroventricularly (icv) with omega-ctx, and hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx (0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior, complex thermoregulatory changes, and motor deficits lasting up to 48 h. Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less than 0.05) associated with increased circulating levels of norepinephrine and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory shock and death. Central administration of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg), neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100 nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type Ca2(+)-channel blockers, respectively, did not cause any behavioral or hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg icv) caused a mild transient pressor response. Pretreatment with the gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined intravenous pretreatment with propranolol and N-methylatropine blocked the omega-ctx effects. Our data suggest that omega-ctx actions in the brain involve central GABAergic mechanisms modulated by yet a different type of Ca2+ channels not characterized by any of the known voltage-operated Ca2+ channels.

scholarly journals Activation of the Y1 Receptor by Neuropeptide Y Regulates the Growth of Prostate Cancer Cells

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1466-1473 ◽  
Author(s):  
Massimiliano Ruscica ◽  
Elena Dozio ◽  
Stéphane Boghossian ◽  
Giorgio Bovo ◽  
Vera Martos Riaño ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neuropeptide Y ◽  
Cell Lines ◽  
Y1 Receptor ◽  
Intracellular Signals ◽  
Relevant Role ◽  
Pc3 Cells ◽  
Du145 Cells ◽  
Kinetics Of

This study deals with the role of neuropeptide Y (NPY) in the regulation of cell proliferation. NPY is expressed in the normal and tumoral prostate, but no data on its possible role in prostate cancer (PCa) progression are available. Therefore, we evaluated the direct effect of NPY on the growth of the human PCa cell lines LNCaP (androgen dependent) and DU145 and PC3 (androgen independent). All PCa cell lines expressed Y1-R gene and protein. NPY treatment reduced the proliferation of LNCaP and DU145 cells and increased that of PC3 cells. The Y1-R antagonist BIBP3226 abolished such effects, suggesting a mandatory role of Y1-R in this process. LNCaP cells showed elevated constitutive levels of phosphorylated ERK1/2, which were not affected by NPY. In DU145 cells, NPY stimulated a long-lasting ERK1/2 activation, whereas, in PC3 cells, this effect was rapid and transient and required activation of protein kinase C. Moreover, in both cell lines, pretreatment with BIBP3226 prevented the NPY-induced ERK1/2 phosphorylation, further supporting Y1-R involvement. NPY treatment reduced forskolin-stimulated cAMP accumulation only in PC3 cells and did not change intracellular calcium concentration in any PCa cell line. These data indicate that NPY may directly regulate PCa cell growth via Y1-R. The direction of this effect appears to be related to the time kinetics of MAPK activation, i.e. long-lasting vs. transient, and to the clone-specific involvement of other intracellular signals. These findings suggest that NPY-related mechanisms might play a relevant role in the progression of PCa, at both androgen dependent and independent stages.

scholarly journals Role of the Y1 Receptor in the Regulation of Neuropeptide Y-Mediated Feeding: Comparison of Wild-Type, Y1 Receptor-Deficient, and Y5 Receptor-Deficient Mice

Endocrinology ◽  
2000 ◽  
Vol 141 (3) ◽  
pp. 1011-1016 ◽  
Author(s):  
Akio Kanatani ◽  
Satoshi Mashiko ◽  
Naomi Murai ◽  
Nami Sugimoto ◽  
Junko Ito ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Wild Type ◽  
Y1 Receptor ◽  
Deficient Mice

scholarly journals Chemical modification of neuropeptide Y for human Y1 receptor targeting in health and disease

2019 ◽  
Vol 400 (3) ◽  
pp. 299-311 ◽  
Author(s):  
Sven Hofmann ◽  
Kathrin Bellmann-Sickert ◽  
Annette G. Beck-Sickinger
Keyword(s):  
Neuropeptide Y ◽  
Peptide Yy ◽  
Peptide Hormone ◽  
Receptor Subtypes ◽  
Innovative Strategies ◽  
Y1 Receptor ◽  
Physiological Processes ◽  
Health And Disease ◽  
Innovative Drugs ◽  
G Protein Coupled

AbstractAs a very abundant neuropeptide in the brain and widely distributed peptide hormone in the periphery, neuropeptide Y (NPY) appears to be a multisignaling key peptide. Together with peptide YY, pancreatic polypeptide and the four human G protein-coupled receptor subtypes hY1R, hY2R, hY4R and hY5R it forms the NPY/hYR multiligand/multireceptor system, which is involved in essential physiological processes as well as in human diseases. In particular, NPY-induced hY1R signaling plays a central role in the regulation of food intake and stress response as well as in obesity, mood disorders and cancer. Thus, several hY1R-preferring NPY analogs have been developed as versatile tools to unravel the complex NPY/hY1R signaling in health and disease. Further, these peptides provide basic lead structures for the development of innovative drugs. Here, the current research is summarized focusing on the development of differently sized hY1R-preferring NPY analogs as well as their advances with respect to hY1R profiling, potential therapeutic applications and targeted cancer imaging and therapy. Finally, major limitations and innovative strategies for next generation hY1R-preferring NPY analogs are addressed.

Hypothalamic neuropeptide Y inhibits gastric acid output in rat: role of the autonomic nervous system

1992 ◽  
Vol 263 (5) ◽  
pp. G726-G732 ◽  
Author(s):  
G. A. Humphreys ◽  
J. S. Davison ◽  
W. L. Veale
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Neuropeptide Y ◽  
Gastric Acid ◽  
Acid Output ◽  
Gastric Acid Output ◽  
Autonomic Nervous ◽  
Anesthetized Rats ◽  
Antisecretory Effect

Injection of neuropeptide Y (NPY) into the hypothalamic paraventricular nucleus (PVN) inhibits gastric acid secretion in anesthetized rats. The role of the autonomic nervous system in mediation of this response was investigated. Unilateral microinjection of 200 pmol NPY into the PVN of anesthetized rats inhibited spontaneous and pentagastrin-stimulated gastric acid output. Inhibition was abolished by subdiaphragmatic vagotomy, atropine, and bethanechol but was restored by electrical stimulation of the distal cut end of the vagus in cervically vagotomized rats. Although sympathectomy, phenoxybenzamine, and yohimbine abolished the inhibition, it was not affected by prazosin treatment. Gastric blood flow was not altered by injection of NPY. These results suggest that the antisecretory effect of NPY in the PVN was sympathetically mediated via suppression of gastric vagal cholinergic tone through activation of alpha 2-adrenoceptors.

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