Role of serotonin3 receptors in the nucleus tractus solitarii on the carotid chemoreflex

1997 ◽  
Vol 272 (3) ◽  
pp. H1250-H1259 ◽  
Author(s):  
C. Sevoz ◽  
J. C. Callera ◽  
B. H. Machado ◽  
M. Hamon ◽  
R. Laguzzi
Keyword(s):  
Inhibitory Effect ◽  
Nucleus Tractus Solitarii ◽  
Inhibitory Influence ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Receptor Stimulation ◽  
Gaba A ◽  
Anesthetized Rats ◽  
Carotid Body Chemoreceptors ◽  
Spontaneously Breathing

The effects of serotonin3 (5-HT3)-receptor stimulation in the nucleus tractus solitarii (NTS) on the cardiovagal, sympathetic, and respiratory responses to activation of carotid body chemoreceptors were investigated in anesthetized rats. The chemoreflex responses were triggered by an intravenous administration of KCN (40 microg/kg) in spontaneously breathing urethan-chloralose-anesthetized rats or by an intracarotid administration of saline saturated with 100% CO2 in pancuronium bromide-paralyzed and artificially ventilated urethan-anesthetized rats. Microinjections of 5-HT (2.5-5 nmol) or the 5-HT3 agonist 1-(m-chlorophenyl)-biguanide (CPBG, 300-1,200 pmol) into the commissural NTS blocked in a dose-dependent manner the atropine-sensitive chemoreflex bradycardia elicited by KCN. However, neither 5-HT nor CPBG affected the KCN-induced increase in respiratory volume and the CO2-induced increases in blood pressure and lumbar sympathetic nerve discharge. The inhibitory effect of 5-HT or CPBG on KCN-induced bradycardia was blocked by prior intra-NTS microinjection of a 5-HT3 antagonist, such as zacopride (100 pmol) or ondansetron (100 pmol), or the A-type gamma-aminobutyric acid (GABA(A)) antagonist bicuculline (10 pmol). In contrast, local microinjections of antagonists acting at 5-HT1 and 5-HT2 receptors, such as methysergide (100 pmol) and ketanserin (10 pmol), respectively, did not prevent the actions of 5-HT or CPBG. These data show that the stimulation of 5-HT3 receptors in the NTS exerted an inhibitory influence, probably through the activation of a local GABAergic system, on the cardiovagal component of the chemoreflex. Because similar effects of 5-HT3-receptor stimulation in the NTS were previously found on the baroreflex and Bezold-Jarisch reflex responses, it can be inferred that NTS 5-HT3 receptors play a key modulatory role in the reflex control of the heart rate.

Halothane Selectively Inhibits Nonshivering Thermogenesis 

1995 ◽  
Vol 82 (2) ◽  
pp. 491-501 ◽  
Author(s):  
Andrea Dicker ◽  
Kerstin B. E. Ohlson ◽  
Lennart Johnson ◽  
Barbara Cannon ◽  
Sten G.E. Lindahl ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Inhibitory Effect ◽  
Nonshivering Thermogenesis ◽  
Halothane Anesthesia ◽  
Control Series ◽  
Mechanically Ventilated ◽  
Anesthetized Rats ◽  
Rate Of Oxygen Consumption ◽  
Spontaneously Breathing ◽  
Thermogenic Response

Background During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia. Methods The rate of oxygen consumption was measured in cold-acclimated hamsters and rats. The rate evoked by norepinephrine injection in hamsters at an environmental temperature of approximately 24 degrees C was used as a measure of the capacity for nonshivering thermogenesis. Anesthesia was induced by 3% halothane and maintained by 1.5% halothane. One experimental series with spontaneously breathing hamsters and a second control series with spontaneously breathing rats and with rats whose lungs were mechanically ventilated were conducted. Results Norepinephrine injection led to a fourfold increase in the rate of oxygen consumption in control hamsters; after this response had subsided, a second injection led to a similar effect. Halothane anesthesia caused an approximately 20% decrease in resting metabolic rate (P < 0.05) and a 70% inhibition of the thermogenic response to norepinephrine (P < 0.001). The halothane concentration yielding half-maximal inhibitory effect was estimated to be less than 1.0%. After the animals had recovered from halothane anesthesia, a completely restored thermogenic response to norepinephrine was observed. The inhibitory effect of halothane also was observed in hamsters maintained at normothermia and was therefore not secondary to the slight hypothermia that otherwise developed during anesthesia. In a series of control experiments, it was confirmed that rats also showed large thermogenic responses to norepinephrine injections, and it was found that, in spontaneously breathing halothane-anesthetized rats, the thermogenic response to norepinephrine was also much inhibited. Further, in halothane-anesthetized rats whose lungs were mechanically ventilated, and where blood gases were kept at virtually normal levels, the thermogenic response to norepinephrine was found to be similarly markedly inhibited. Conclusions A much diminished or abolished thermogenic response to injected norepinephrine was demonstrated in halothane-anesthetized animals. This implies that there would be a diminished ability to elicit nonshivering thermogenesis even when this process is physiologically induced. Such a diminished ability could in part explain the susceptibility of neonates and infants to hypothermia during halothane anesthesia.

Dose-dependent Enhancement of In Vivo  GABAA–Benzodiazepine Receptor Binding by Isoflurane

2001 ◽  
Vol 95 (3) ◽  
pp. 585-593 ◽  
Author(s):  
Ferenc E. Gyulai ◽  
Mark A. Mintun ◽  
Leonard L. Firestone
Keyword(s):  
Minimum Alveolar Concentration ◽  
Distribution Volume ◽  
T Test ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
General Anesthetics ◽  
Gaba A ◽  
Site Density ◽  
Dose Dependent

Background Abundant in vitro and animal model data suggest the postsynaptic gamma-aminobutyric acid receptor type A (GABA(A)-R) is an important target for volatile general anesthetics, but the relevance of these models is untested in humans. Because benzodiazepines have also been shown to act via a specific GABA(A)-R site, they provide sensitive probes for the GABA(A)-R. Availability of the 11C-labeled benzodiazepine ligand, flumazenil, allowed us to quantitatively test in humans whether the volatile anesthetic isoflurane affects GABA(A)-Rs in vivo in a dose-dependent manner. Methods 11C-flumazenil positron emission tomography scans were obtained in 12 healthy subjects while awake (control condition) and anesthetized with either 1.0 or 1.5 minimum alveolar concentration isoflurane (n = 7 and 5, respectively; isoflurane conditions). Regions of interest included areas of high, intermediate, and low GABA(A)-benzodiazepine site density. For each subject and experimental condition, the binding of 11C-flumazenil, expressed as distribution volume (which linearly correlates to maximal binding site density and apparent ligand affinity), was obtained by curve fitting using a two-compartment model. Results The ratio of distribution volume increased significantly in each examined region during the isoflurane conditions compared with control conditions (P < 0.01, one-tailed t test). Furthermore, the increases in ratio of distribution volume during the 1.5-minimum alveolar concentration isoflurane condition were significantly greater than those measured during 1.0 minimum alveolar concentration isoflurane inhalation (P < 0.002, one-tailed t test). Conclusions Isoflurane exposure appeared to enhance receptor-specific 11C-flumazenil binding in a dose-dependent manner. The results suggest the possibility that a conformational change of the GABA(A)-R is involved in the mechanism of action of isoflurane in the living human brain.

Inhibitory effect of phorbol ester on sodium transport in frog urinary bladder

1990 ◽  
Vol 259 (3) ◽  
pp. F425-F431
Author(s):  
T. Satoh ◽  
H. Endou
Keyword(s):  
Urinary Bladder ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Inhibitory Effect ◽  
Inhibitory Influence ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Frog Urinary Bladder ◽  
Na Transport

To confirm the role of protein kinase C (PKC) on epithelial Na transport, we studied the effects of phorbol 12-myristate 13-acetate (PMA) and dioctanoylglycerol (DiC8), activators of PKC, on short-circuit current (Isc) in frog urinary bladder and further examined the influence of sphingosine, an inhibitor of PKC, on PMA- or DiC8-modulated Isc. PMA reduced basal Isc in a dose-dependent manner, and sphingosine (10 and 100 microM) partially restored PMA-reduced Isc. On the other hand, DiC8 (5 x 10(-5) M) also reduced basal Isc, and this action was completely prevented by 100 microM sphingosine. Both PMA (4 x 10(-5) M) and DiC8 inhibited vasopressin (50 mU/ml)- and forskolin (5 x 10(-5) M)-stimulated increases in Isc. PMA (4 x 10(-5) M) also inhibited 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP)-stimulated increase in Isc. Furthermore, PMA (4 x 10(-5) M) and DiC8 (5 x 10(-5) M) inhibited vasopressin (50 mU/ml)-stimulated cAMP accumulation. DiC8 also inhibited forskolin-stimulated cAMP accumulation. These results indicate that PMA exerts inhibitory influence on Na transport mainly by its own potency of PKC activation. In addition, it is suggested that there is a cross talk in epithelial Na transport between PKC and cAMP-dependent pathway in frog urinary bladder.

Neopterin-induced Suppression of Erythropoietin Production In Vitro

Pteridines ◽  
1995 ◽  
Vol 6 (1) ◽  
pp. 12-16 ◽  
Author(s):  
W. Schobersberger ◽  
W. Jelkmann ◽  
J. Fandrey ◽  
S. Frede ◽  
H. Wachter ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Inhibitory Influence ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Anemia Of Chronic Disease ◽  
Erythropoietin Production ◽  
High Concentrations ◽  
Dose Dependent

Summary The production of neopterin increases in several diseases with activation of the ceIlular immune response. As previously shown serum concentrations of neopterin are inversely correlated with blood hemoglobin concentrations in the anemia of hematological and malignant disorders. Besides the role of chronic immune activation on the disturbed iron metabolism, an inhibitory influence of pteridines on cellular erythropoietin production could not be excluded. To test the possibility that pteridines are able to suppress the hypoxia-induced production of erythropoietin, the effects of neopterin and 7,8-dihydroneopterin on the human ceIl line HepG2 (hepatoceIlular carcinoma) were investigated. 24 h incubation with neopterin induced a dose-dependent reduction of erythropoietin production. The erythropoietin concentration significantly decreased by - 57.6% with 300 11M and by - 34.9% with 100 11M neopterin, respectively. 7,8 dihydroneopterin did not influence erythropoietin production. The inhibitory effect of neopterin on erythropoietin production was a consequence of reduced erythropoietin-mRNA levels. The results of this study show a neopterin-induced suppression of hypoxia-induced erythropoietin formation in HepG2 cultures in a dose dependent manner. We speculate that under in vivo conditions high concentrations of neopterin can aggravate the anemia of chronic disease.

Medullary vasomotor activity and hypoxic sympathoexcitation in pentobarbital-anesthetized rats

1996 ◽  
Vol 270 (2) ◽  
pp. R348-R355 ◽  
Author(s):  
M. K. Sun ◽  
D. J. Reis
Keyword(s):  
Arterial Pressure ◽  
Acute Hypoxia ◽  
Control Level ◽  
Sympathetic Nerves ◽  
Intrathecal Administration ◽  
Reticular Nucleus ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Anesthetized Rats ◽  
Pressor Responses

In pentobarbital sodium-anesthetized, paralyzed, and ventilated rats, systemic hypoxia, produced by intratracheal N2 administration for 20 s, rapidly increased activities of reticulospinal vasomotor neurons in the rostroventolateral reticular nucleus (RVL) of the medulla oblongata (by 23.9 +/- 4.7 spikes/s) and sympathetic nerves (by 30.9 +/- 4.7 microV) and arterial pressure (by 35.6 +/- 6.4 mmHg). The sympathoexcitatory and pressor responses were abolished by bilateral microinjections of muscimol, a gamma-aminobutyric acid (GABA)A-receptor agonist, (250 pmol per 50 nl/site) into the RVL. Chemical inhibition of RVL also reduced arterial pressure to 48.1 +/- 3.7 mmHg and eliminated sympathetic nerve activity. Intravenous infusion of L-phenylephrine and intrathecal administration of kainic acid restored arterial pressure to control level but not the rapid sympathoexcitatory responses to acute hypoxia. We conclude that, in pentobarbital-anesthetized rats, the sympathetic vasomotor tone and pressor responses to acute hypoxia depend on activity and excitation of RVL-spinal vasomotor neurons. The neural mechanisms responsible for the sympathetic tone and rapid pressor responses to hypoxia in these animals qualitatively differ neither from those anesthetized with urethan nor from the decerebrate unanesthetized animals.

Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in anesthetized rats

1996 ◽  
Vol 81 (6) ◽  
pp. 2349-2357 ◽  
Author(s):  
Lu-Yuan Lee ◽  
Robert F. Morton ◽  
Jan M. Lundberg
Keyword(s):  
Lactic Acid ◽  
Intravenous Injection ◽  
Inhibitory Effect ◽  
Electrophysiological Recording ◽  
Vagus Nerves ◽  
C Fibers ◽  
Anesthetized Rats ◽  
C Fiber ◽  
Intense Burst ◽  
Carotid Body Chemoreceptors

Lee, Lu-Yuan, Robert F. Morton, and Jan M. Lundberg.Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in anesthetized rats. J. Appl. Physiol. 81(6): 2349–2357, 1996.—Experiments were carried out to characterize the cardiorespiratory reflex responses to intravenous injection of lactic acid and to determine the involvement of vagal bronchopulmonary C-fiber afferents in eliciting these responses in anesthetized rats. Bolus injection of lactic acid (0.2 mmol/kg iv) immediately elicited apnea, bradycardia, and hypotension, which were then followed by a sustained hyperpnea. The immediate apneic and bradycardiac responses to lactic acid were completely abolished by bilateral vagotomy and were absent when the same dose of lactic acid was injected into the left ventricle. The subsequent hyperpneic response was substantially attenuated by denervation of carotid body chemoreceptors. After a perineural capsaicin treatment of both vagus nerves to block the conduction of C fibers, lactic acid no longer evoked the immediate apnea and bradycardia, whereas the hyperpneic response became more pronounced and sustained, presumably because of the removal of the inhibitory effect on breathing mediated by pulmonary C-fiber activation. Single-unit electrophysiological recording showed that intravenous injection of lactic acid consistently evoked an abrupt and intense burst of discharge from the vagal C-fiber afferent endings in the lungs. In conclusion, the cardiorespiratory depressor responses induced by lactic acid are predominantly elicited by activation of vagal pulmonary C fibers.

Effects of amino acid neurotransmitters on spontaneous muscular activity of the rumen amphistome, Gastrothylax crumenifer

2009 ◽  
Vol 83 (4) ◽  
pp. 385-389 ◽  
Author(s):  
P.K. Verma ◽  
D. Kumar ◽  
S.K. Tandan
Keyword(s):  
Amino Acid ◽  
Muscular Activity ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Helminth Parasites ◽  
Gamma Aminobutyric Acid ◽  
Amino Acid Neurotransmitters ◽  
Concentration Dependent Manner ◽  
Gastrothylax Crumenifer ◽  
Spontaneous Contractions

AbstractAmino acid neurotransmitters play an important role in regulating neuromuscular activity of helminth parasites. The present study aimed to investigate the effects of different amino acid neurotransmitters [l-glutamate, glycine, gamma-aminobutyric acid (GABA)] on spontaneous muscular activity of isometrically mounted Gastrothylax crumenifer. l-Glutamate caused a significant increase in the amplitude and frequency of spontaneous contractions of rumen fluke at 10− 7–10− 4 m and at 10− 5–10− 4 m concentrations, respectively. Glycine application (10− 7–10− 3 m) produced a significant decrease in the amplitude and frequency of spontaneous muscular contractions in a concentration-dependent manner, as compared to control amplitude (0.53 ± 0.02 g) and frequency (51 ± 4.65/5 min). Similarly, GABA produced a significant (P < 0.05) decrease in amplitude, baseline tension and frequency of spontaneous muscular contractions of G. crumenifer. To further substantiate the GABA effect, GABAA receptor antagonists, picrotoxin and bicuculline were applied. Picrotoxin (10− 5–10− 3 m) caused a significant (P < 0.05) increase in amplitude, baseline tension and frequency of the rumen fluke as compared to control; whereas bicuculline did not elicit any observable effect in these attributes in isometrically mounted rumen flukes. These observations suggested that l-glutamate has an excitatory, whereas GABA and glycine have an inhibitory, effect on the spontaneous muscular activity of G. crumenifer.

scholarly journals Acute neurosteroid modulation and subunit isolation of the gamma-aminobutyric acidA receptor in the bullfrog, Rana catesbeiana

2004 ◽  
Vol 32 (3) ◽  
pp. 921-934 ◽  
Author(s):  
DM Hollis ◽  
FW Goetz ◽  
SB Roberts ◽  
SK Boyd
Keyword(s):  
Rana Catesbeiana ◽  
Specific Binding ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Binding Studies ◽  
Pregnenolone Sulfate ◽  
Brain Membrane ◽  
Gaba A ◽  
Muscimol Binding

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has multiple receptors. In mammals, the GABA(A) receptor subtype is modulated by neurosteroids. However, whether steroid interaction with the GABA(A) receptor is unique to mammals or a conserved feature in vertebrates is unknown. Thus, neurosteroid modulation of the GABA(A) receptor was investigated in the brain of the bullfrog (Rana catesbeiana) using the mammalian GABA(A) receptor agonist [(3)H]muscimol. Two neurosteroids, allopregnanolone and pregnenolone sulfate, affected [(3)H]muscimol specific binding in bullfrog brain membrane preparations. Allopregnanolone significantly increased [(3)H]muscimol specific binding in a dose- and time-dependent manner. The pattern of allopregnanolone modulation supports the hypothesis that the bullfrog brain possesses both high-affinity and low-affinity [(3)H]muscimol binding sites. Unlike allopregnanolone, pregnenolone sulfate showed biphasic modulation with increased [(3)H]muscimol specific binding at low nanomolar concentrations and decreased specific binding at micromolar concentrations. Additionally, three cDNA fragments with significant homology to mammalian GABA(A) receptor subunits were isolated from the bullfrog brain. These fragments belong to the alpha1, beta1, and gamma2 subunit families. In mammals, GABA(A) receptors composed of these specific subunit isoforms are effectively modulated by neurosteroids, including allopregnanolone. Neurosteroid modulation of the amphibian brain GABA(A) receptor is therefore supported by both [(3)H]muscimol binding studies and subunit sequences. Allopregnanolone and pregnenolone sulfate modulation of this receptor may thus represent a significant mechanism for steroid influence on amphibian brain and behavior.

scholarly journals Inhibitory effect of tetramethylpyrazine combined with propranolol on murine hemangioma endothelial cells

2021 ◽  
Vol 18 (4) ◽  
pp. 721-726
Author(s):  
Wan-Wan Jin ◽  
Jian-Ming Wu ◽  
Yi Tong ◽  
Ji-Cong Jiang ◽  
Hehe Quan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Endothelial Cells ◽  
Cell Apoptosis ◽  
Mammalian Target Of Rapamycin ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Inhibitory Influence ◽  
Dependent Manner ◽  
Signal Route

Purpose: To study the inhibitory effect of different doses of tetramethylpyrazine (TMP) combined with the beta-blocker, propranolol (Pro) on hemangioma endothelial (EOMA) cells. Methods: EOMA cells were cultured in vitro with varying doses of TMP and Pro (5, 10, 20 and 40 uM). The effect of treatments on cell proliferation was assessed by MTT assay, while cell apoptosis was assayed by flow cytometry. The expressions of Bcl-2, Bax, p-mTOR), total-mammalian target of rapamycin (t-mTOR, p-p70S6) and total-p70 ribosomal protein S6 (t-p70S6) proteins were determined using Western blot. Results: MTT data showed that when used alone, TMP had no significant inhibitory effect on EOMA cells (p > 0.05). However, when TMP was combined with propranolol, there was significant inhibition of EOMA cells, and that the inhibition is dependent on TMP dose. Flow cytometry results showed that the combination of TMP and Pro induced EOMA cell apoptosis dose-dependently (p < 0.05). Moreover, TMP dose-dependently inhibited the phosphorylation of mTOR and p70S6 in EOMA cells, and enhanced Bax expression, but downregulated Bcl-2 (p < 0.05). Conclusion: These results suggest that TMP enhances the inhibitory influence of Pro p-mTOR and pp-70S6 in EOMA cells in a dose-dependent manner. Thus, TMP may enhance Pro-induced inhibition of the growth of endothelial cells, and promote apoptosis through suppression of activation of PI3K/AKT signal route. These findings provide a theoretical basis for the clinical application of TMP/Pro combination for the treatment of hemangioma.

Respiratory pattern changes during costovertebral joint movement

1980 ◽  
Vol 48 (5) ◽  
pp. 862-867 ◽  
Author(s):  
R. Shannon
Keyword(s):  
Inhibitory Effect ◽  
Respiratory Pattern ◽  
Nerve Supply ◽  
Joint Movement ◽  
Receptor Stimulation ◽  
Lung Inflation ◽  
Manual Chest Compression ◽  
Costovertebral Joint ◽  
Spontaneously Breathing ◽  
Stimulation Of

Experiments were conducted to determine if costovertebral joint manipulation (CVJM) could influence the respiratory pattern. Phrenic efferent activity (PA) was monitored in dogs that were anesthetized with Dial-urethane, vagotomized, paralyzed, and artificially ventilated. Ribs 6-10 (bilaterally) were cut and separated from ribs 5-11. Branches of thoracic nerves 5-11 were cut, leaving only the joint nerve supply intact. Manual joint movement in an inspiratory or expiratory direction had an inhibitory effect on PA. Sustained displacement of the ribs could inhibit PA for a duration equal to numerous respiratory cycles. CVJM in synchrony with PA resulted in an increased respiratory rate. The inspiratory inhibitory effect of joint receptor stimulation was elicited with manual chest compression in vagotomized spontaneously breathing dogs, but not with artificial lung inflation or deflation. It is concluded that the effect of CVJM on the respiratory pattern is due to stimulation of joint mechanoreceptors, and that they exert their influence in part via the medullary-pontine rhythm generator.

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