scholarly journals The role of spinal GABAergic circuits in the control of phrenic nerve motor output

2015 ◽  
Vol 308 (11) ◽  
pp. R916-R926 ◽  
Author(s):  
Vitaliy Marchenko ◽  
Michael G. Z. Ghali ◽  
Robert F. Rogers
Keyword(s):  
Phrenic Nerve ◽  
Physiological Role ◽  
Ventral Horn ◽  
Motor Output ◽  
Respiratory Pattern ◽  
Adult Rats ◽  
Spinal Circuitry ◽  
Phrenic Nucleus ◽  
Nerve Recordings

While supraspinal mechanisms underlying respiratory pattern formation are well characterized, the contribution of spinal circuitry to the same remains poorly understood. In this study, we tested the hypothesis that intraspinal GABAergic circuits are involved in shaping phrenic motor output. To this end, we performed bilateral phrenic nerve recordings in anesthetized adult rats and observed neurogram changes in response to knocking down expression of both isoforms (65 and 67 kDa) of glutamate decarboxylase (GAD65/67) using microinjections of anti-GAD65/67 short-interference RNA (siRNA) in the phrenic nucleus. The number of GAD65/67-positive cells was drastically reduced on the side of siRNA microinjections, especially in the lateral aspects of Rexed's laminae VII and IX in the ventral horn of cervical segment C4, but not contralateral to microinjections. We hypothesize that intraspinal GABAergic control of phrenic output is primarily phasic, but also plays an important role in tonic regulation of phrenic discharge. Also, we identified respiration-modulated GABAergic interneurons (both inspiratory and expiratory) located slightly dorsal to the phrenic nucleus. Our data provide the first direct evidence for the existence of intraspinal GABAergic circuits contributing to the formation of phrenic output. The physiological role of local intraspinal inhibition, independent of descending direct bulbospinal control, is discussed.

Development of sensitivity to cAMP-inducing hormones in the rat stomach

1984 ◽  
Vol 247 (3) ◽  
pp. G231-G239
Author(s):  
C. Gespach ◽  
Y. Cherel ◽  
G. Rosselin
Keyword(s):  
Biological Activities ◽  
Physiological Role ◽  
H2 Receptor Antagonist ◽  
Adult Rats ◽  
Gastric Glands ◽  
Camp Generation ◽  
Final Maturation ◽  
Noncompetitive Inhibitor ◽  
Regulatory Properties

Development of cAMP responses to secretin, pancreatic glucagon, and histamine was measured in gastric glands of fetal (day 20), postnatal (days 1-30), and adult rats (day 65). cAMP stimulation by these hormones was already detected on day 20 of gestation. cAMP generation showed biphasic variations during the 1st days of life and at the onset of weaning (day 20). Anticipated weaning at day 14 triggered precocious maturation (efficacies) of the cAMP-generating systems sensitive to secretin, glucagon, and histamine without changing the potencies of the hormones. During development, the general characteristics (potency and pharmacological or regulatory properties) of the receptor-cAMP systems studied were comparable with those evidenced in adult rats. At days 5, 20, and 65, vasoactive intestinal peptide and the peptide having N-terminal histidine and C-terminal isoleucine amide (PHI) were about 100 times less potent than secretin (EC50 = 1.5 X 10(-9) M secretin). The histamine action could be blocked by the competitive H2-receptor antagonist cimetidine (70-100% inhibition) as well as by the noncompetitive inhibitor somatostatin (37-62% inhibition). The data indicate that these regulatory hormones (secretin, glucagon(s), histamine, and somatostatin) might have a direct effect on gastric glands and may modulate their biological activities (metabolism, differentiation, proliferation, and exocrine and endocrine secretions) from the neonatal period in rats. The important physiological role of weaning on the final maturation of the cAMP-generating systems in rat gastric glands is underlined.

Naloxone enhances respiratory output in cats

1979 ◽  
Vol 47 (5) ◽  
pp. 1105-1111 ◽  
Author(s):  
E. E. Lawson ◽  
T. G. Waldrop ◽  
F. L. Eldridge
Keyword(s):  
Phrenic Nerve ◽  
Opiate Receptors ◽  
Physiological Role ◽  
Opiate Antagonist ◽  
Nerve Activity ◽  
Phrenic Nerve Activity ◽  
End Tidal ◽  
Decerebrate Cats ◽  
End Tidal Co2

To investigate the physiological role of opiate receptors and opiatelike neurotransmitters, which are present in brain-stem respiratory centers, we administered naloxone to 10 cats by intravenous injection. These animals were vagotomized, paralyzed, and servo-ventilated to maintain constant end-tidal CO2; in addition, their carotid sinus nerves were sectioned bilaterally. Respiratory output was assessed by integration of phrenic nerve activity. Control saline infusions had no effect on respiratory output. However, administration of naloxone (0.4 mg/kg) caused phrenic minute output to increase significantly in each of five anesthetized cerebrate cats (control 7,272 +/- 1,615 U/min; 30 min postnaloxone 12,920 +/- 3,857 U/min; P less than 0.05) and five unanesthetized decerebrate cats (control 10,368 +/- 1,222 U/min; naloxone 14,648 +/- 3,225 U/min; P less than 0.05). In addition to the effect on phrenic minute output, naloxone infusion resulted in an increase of the inspiratory rate of rise of phrenic nerve activity in each cat. There was no change in the ratio of inspiratory duration to total respiratory period (TI/Ttot). Because naloxone is a specific opiate antagonist, we suggest that endogenous opiatelike neurotransmitters (endorphins) may modulate central inspiratory drive.

Role of deflation-sensitive feedback in control of end-expiratory volume in rats

1993 ◽  
Vol 75 (2) ◽  
pp. 902-911 ◽  
Author(s):  
M. Sammon ◽  
J. R. Romaniuk ◽  
E. N. Bruce
Keyword(s):  
Respiratory Pattern ◽  
Electromyographic Activity ◽  
Phase Switching ◽  
Inspiratory Muscles ◽  
Tracheal Pressure ◽  
Posterior Cricoarytenoid ◽  
Lung Deflation ◽  
Nerve Recordings ◽  
Thyroarytenoid Muscle

Rats breathing from reduced end-expiratory volumes (EEV) exhibit transient bursting of inspiratory airflow local to the expiratory-inspiratory transition (E-I) accompanied by increases in inspiration-to-expiration duration ratio. Continuous positive (CPAP) and negative (CNAP) airway pressures (+3 to -9 cmH2O) were applied to tracheal openings of 17 unilaterally vagotomized rats (urethan anesthetized) to evaluate the feedback mechanisms associated with these oscillatory "expiratory interrupts." Whole nerve recordings of afferent vagus (Vag) were primarily inspiratory with CPAP. As tracheal pressure was reduced in a stepwise manner, progressive decreases in inspiratory peaks and increases in activity during late expiration were seen on Vag. Single-fiber recordings correlate Vag expiratory activity with slowly adapting receptors sensitive to lung deflation. With CNAP, 1) progressively earlier onsets of activity in inspiratory muscles (e.g., diaphragm, genioglossus, posterior cricoarytenoid) were observed (increased inspiratory duration, decreased expiratory duration); oscillations at E-I developed only when expiratory peaks on Vag were significant. 2) Thyroarytenoid muscle exhibited onset of electromyographic activity that immediately succeeded onset of Vag during late expiration. When the trachea is intact, these two actions might combine to produce a respiratory pattern similar to the "grunting" often seen in newborns breathing from reduced EEVs. In contrast to larger mammals, rats rely strongly on deflation reflexes for control of E-I phase switching, presumably to aid in maintenance of an elevated EEV.

Liposome-mediated macrophage depletion: an experimental approach to study the role of testicular macrophages in the rat

1993 ◽  
Vol 136 (3) ◽  
pp. 407-NP ◽  
Author(s):  
A. Bergh ◽  
J.-E. Damber ◽  
N. van Rooijen
Keyword(s):  
Leydig Cell ◽  
Cell Function ◽  
Physiological Role ◽  
Adult Rats ◽  
Testosterone Secretion ◽  
Testicular Weight ◽  
The Right ◽  
Leydig Cell Function ◽  
Testicular Macrophages

ABSTRACT Liposome-entrapped dichloromethylene diphosphonate was injected locally into the right testes of adult rats. This treatment, which has been found to deplete resident macrophages in some other organs, reduced the number of testicular macrophages by at least 90%. Testicular weight and seminiferous tubule morphology were unaffected by liposome treatment. Leydig cell testosterone secretion gradually declined in the macrophage-depleted testes, and there was a compensatory increase in Leydig cell size and testosterone secretion in the contralateral saline-injected testes. These observations suggest that macrophages influence Leydig cell function locally. It is concluded that liposome-mediated depletion of testicular macrophages may serve as an experimental model with which to study the physiological role of these cells. Journal of Endocrinology (1993) 136, 407–413

Physiological Role of Cyclic Electron Flow in Higher Plants

2012 ◽  
Vol 30 (1) ◽  
pp. 100
Author(s):  
Wei HUANG ◽  
Shi-Bao ZHANG ◽  
Kun-Fang CAO
Keyword(s):  
Higher Plants ◽  
Electron Flow ◽  
Physiological Role ◽  
Cyclic Electron Flow

The Renal Outer Medullary Potassium Channel (ROMK): An Intriguing Pharmacological Target for an Innovative Class of Diuretic Drugs

2018 ◽  
Vol 25 (23) ◽  
pp. 2627-2636 ◽  
Author(s):  
Vincenzo Calderone ◽  
Alma Martelli ◽  
Eugenia Piragine ◽  
Valentina Citi ◽  
Lara Testai ◽  
...  
Keyword(s):  
Physiological Role ◽  
Clinical Use ◽  
Diuretic Activity ◽  
First Line ◽  
Potassium Homeostasis ◽  
Diuretic Drugs ◽  
Pharmacological Target ◽  
Diuretic Agents ◽  
Effective Drugs

In the last four decades, the several classes of diuretics, currently available for clinical use, have been the first line option for the therapy of widespread cardiovascular and non-cardiovascular diseases. Diuretic drugs generally exhibit an overall favourable risk/benefit balance. However, they are not devoid of side effects. In particular, all the classes of diuretics cause alteration of potassium homeostasis. <p> In recent years, understanding of the physiological role of the renal outer medullary potassium (ROMK) channels, has shown an intriguing pharmacological target for developing an innovative class of diuretic agents: the ROMK inhibitors. This novel class is expected to promote diuretic activity comparable to (or even higher than) that provided by the most effective drugs used in clinics (such as furosemide), with limited effects on potassium homeostasis. <p> In this review, the physio-pharmacological roles of ROMK channels in the renal function are reported, along with the most representative molecules which have been currently developed as ROMK inhibitors.

scholarly journals Caspase-14—From Biomolecular Basics to Clinical Approach. A Review of Available Data

2021 ◽  
Vol 22 (11) ◽  
pp. 5575
Author(s):  
Agnieszka Markiewicz ◽  
Dawid Sigorski ◽  
Mateusz Markiewicz ◽  
Agnieszka Owczarczyk-Saczonek ◽  
Waldemar Placek
Keyword(s):  
Cell Death ◽  
Physiological Role ◽  
Skin Barrier ◽  
Clinical Aspects ◽  
Clinical Approach ◽  
Search Term ◽  
Caspase Family ◽  
Skin Conditions ◽  
Theoretical Science

Caspase-14 is a unique member of the caspase family—a family of molecules participating in apoptosis. However, it does not affect this process but regulates another form of programmed cell death—cornification, which is characteristic of the epidermis. Therefore, it plays a crucial role in the formation of the skin barrier. The cell death cycle has been a subject of interest for researchers for decades, so a lot of research has been done to expand the understanding of caspase-14, its role in cell homeostasis and processes affecting its expression and activation. Conversely, it is also an interesting target for clinical researchers searching for its role in the physiology of healthy individuals and its pathophysiology in particular diseases. A summary was done in 2008 by Denecker et al., concentrating mostly on the biotechnological aspects of the molecule and its physiological role. However, a lot of new data have been reported, and some more practical and clinical research has been conducted since then. The majority of studies tackled the issue of clinical data presenting the role of caspase in the etiopathology of many diseases such as retinal dysfunctions, multiple malignancies, and skin conditions. This review summarizes the available knowledge on the molecular and, more interestingly, the clinical aspects of caspase-14. It also presents how theoretical science may pave the way for medical research. Methods: The authors analyzed publications available on PubMed until 21 March 2021, using the search term “caspase 14”.

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