Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit

We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) region has a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. These findings led us to suggest that the cVRG region, and possibly other neural substrates involved in cough regulation, may be sites of action of antitussive drugs. To address this issue, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30–50 nl) of some antitussive drugs into the cVRG of pentobarbital-anesthetized, spontaneously breathing rabbits. [d-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and baclofen at the lower concentrations (0.5 mM and 0.1 mM, respectively) decreased cough number, peak abdominal activity, and peak tracheal pressure and increased cough-related total cycle duration (Tt). At the higher concentrations (5 mM and 1 mM, respectively), both drugs abolished the cough reflex. DAMGO and baclofen also affected baseline respiratory activity. Both drugs reduced peak abdominal activity, while only DAMGO increased Tt, owing to increases in expiratory time. The neurokinin-1 (NK1) receptor antagonist CP-99,994 (10 mM) decreased cough number, peak abdominal activity, and peak tracheal pressure, without affecting baseline respiration. The NK2 receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the cVRG is a site of action of some antitussive agents and support the hypothesis that several neural substrates involved in cough regulation may share this characteristic.

Download Full-text

Modulation of the cough reflex by antitussive agents within the caudal aspect of the nucleus tractus solitarii in the rabbit

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00184.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. R243-R251 ◽

Cited By ~ 49

Author(s):

Donatella Mutolo ◽

Fulvia Bongianni ◽

Elenia Cinelli ◽

Giovanni A. Fontana ◽

Tito Pantaleo

Keyword(s):

Substance P ◽

Receptor Antagonist ◽

Nucleus Tractus Solitarii ◽

Cycle Duration ◽

Cough Reflex ◽

Caudal Portion ◽

Tracheal Pressure ◽

Site Of Action ◽

A Site ◽

Antitussive Agents

We have previously shown that ionotropic glutamate receptors in the caudal portion of the nucleus tractus solitarii (NTS), especially in the commissural NTS, play a prominent role in the mediation of tracheobronchial cough and that substance P potentiates this reflex. This NTS region could be a site of action of some centrally acting antitussive agents and a component of a drug-sensitive gating mechanism of cough. To address these issues, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30–50 nl) of centrally acting antitussive drugs into the caudal NTS of pentobarbitone-anesthetized, spontaneously breathing rabbits. [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and baclofen decreased baseline respiratory frequency because of increases in the inspiratory time only at the higher concentration employed (5 mM and 1 mM, respectively). DAMGO (0.5 mM) and baclofen (0.1 mM) significantly decreased cough number, peak abdominal activity, peak tracheal pressure, and increased cough-related total cycle duration. At the higher concentrations, these agents suppressed the cough reflex. The effects of these two drugs were counteracted by specific antagonists (10 mM naloxone and 25 mM CGP-35348, respectively). The neurokinin-1 (NK1) receptor antagonist CP-99,994 (10 mM) abolished cough responses, whereas the NK2 receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the caudal NTS is a site of action of some centrally acting drugs and a likely component of a neural system involved in cough regulation. A crucial role of substance P release in the mediation of reflex cough is also suggested.

Download Full-text

Suppression of the cough reflex by inhibition of ERK1/2 activation in the caudal nucleus tractus solitarii of the rabbit

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00629.2011 ◽

2012 ◽

Vol 302 (8) ◽

pp. R976-R983 ◽

Cited By ~ 8

Author(s):

Donatella Mutolo ◽

Fulvia Bongianni ◽

Elenia Cinelli ◽

Maria Grazia Giovannini ◽

Tito Pantaleo

Keyword(s):

Tracheobronchial Tree ◽

Nucleus Tractus Solitarii ◽

Cough Reflex ◽

Central Processing ◽

A Site ◽

Short Time ◽

Spontaneously Breathing ◽

Antitussive Agents ◽

Inactive Analog

The caudal nucleus tractus solitarii (cNTS), the predominant site of termination of cough-related afferents, has been shown to be a site of action of some centrally acting antitussive agents. A role of ERK1/2 has been suggested in acute central processing of nociceptive inputs. Because pain and cough share similar features, we investigated whether ERK1/2 activation could also be involved in the central transduction of tussive inputs. For this purpose, we undertook the present research on pentobarbital sodium-anesthetized, spontaneously breathing rabbits by using microinjections (30–50 nl) of an inhibitor of ERK1/2 activation (U0126) into the cNTS. Bilateral microinjections of 25 mM U0126 caused rapid and reversible reductions in the cough responses induced by both mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. In particular, the cough number and peak abdominal activity decreased. Bilateral microinjections of 50 mM U0126 completely suppressed the cough reflex without affecting the Breuer-Hering inflation reflex, the pulmonary chemoreflex, and the sneeze reflex. These U0126-induced effects were, to a large extent, reversible. Bilateral microinjections of 50 mM U0124, the inactive analog of U0126, at the same cNTS sites had no effect. This is the first study that provides evidence that ERK1/2 activation within the cNTS is required for the mediation of cough reflex responses in the anesthetized rabbit. These results suggest a role for ERK1/2 in the observed effects via nontranscriptional mechanisms, given the short time involved. They also may provide hints for the development of novel antitussive strategies.

Download Full-text

Effects of Diphenylether Herbicides on Reactions of Mitochondria and Chloroplasts

Weed Science ◽

10.1017/s0043174500034408 ◽

1970 ◽

Vol 18 (5) ◽

pp. 636-642 ◽

Cited By ~ 44

Author(s):

D. E. Moreland ◽

W. J. Blackmon ◽

H. G. Todd ◽

F. S. Farmer

Keyword(s):

Electron Transport ◽

Oxygen Uptake ◽

Spinacia Oleracea ◽

White Potato ◽

Light Reaction ◽

Site Of Action ◽

Transport Inhibitors ◽

Atp Generation ◽

A Site ◽

Limited Oxygen

Effects of three diphenylether herbicides [2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen); 2,4,6-trichlorophenyl-4′-nitrophenyl ether (hereinafter referred to as MC-1478); and 2,4′-dinitro-4-trifluoromethyl-diphenylether (hereinafter referred to as C-6989)] were measured on phosphorylation and electron transport in spinach(Spinacia oleraceaL.) chloroplasts, and mung bean(Phaseolus aureusL., var. Jumbo) and white potato tuber(Solarium tuberosumL.) mitochondria. All of the diphenylethers acted primarily as inhibitors of chloroplast noncyclic electron transport, and the coupled photophosphorylation. The compounds ranked in the following decreasing order of inhibitory effectiveness: MC-1478 ≥ C-6989 >> nitrofen. A site of action close to light reaction II was suggested. At high molar concentrations, marginal interference with cyclic electron transport or phosphorylation was obtained. In mitochondria, MC-1478 and nitrofen acted primarily as electron transport inhibitors with malate, NADH, and succinate as substrates. MC-1478 was a slightly stronger inhibitor than nitrofen. Only slight stimulation of ADP-limited oxygen uptake was obtained during the oxidation of NADH and succinate; whereas, strong inhibition of oxygen uptake was obtained with malate. C-6989 also weakly stimulated ADP-limited oxygen uptake with NADH and succinate but differed from the two chlorinated diphenylethers in that electron transport was not inhibited when ADP was present in excess. Interference with ATP generation could be one of the mechanisms through which the phytotoxicity of diphenylether herbicides is expressed.

Download Full-text

Harmaline-induced tremor: The benzodiazepine receptor as a site of action

European Journal of Pharmacology ◽

10.1016/0014-2999(80)90020-5 ◽

1980 ◽

Vol 67 (1) ◽

pp. 129-132 ◽

Cited By ~ 35

Author(s):

Harold A. Robertson

Keyword(s):

Benzodiazepine Receptor ◽

Site Of Action ◽

A Site

Download Full-text

Effect of zafirlukast, a leukotriene-receptor antagonist, on cough reflex sensitivity in healthy volunteers: A pilot study

Current Therapeutic Research ◽

10.1016/s0011-393x(00)88535-5 ◽

1999 ◽

Vol 60 (1) ◽

pp. 15-19 ◽

Cited By ~ 3

Author(s):

Peter V. Dicpinigaitis

Keyword(s):

Pilot Study ◽

Healthy Volunteers ◽

Receptor Antagonist ◽

Leukotriene Receptor Antagonist ◽

Cough Reflex Sensitivity ◽

Cough Reflex ◽

Leukotriene Receptor

Download Full-text

Inhibition of Neuropeptide Y (NPY)-Induced Feeding and c-Fos Response in Magnocellular Paraventricular Nucleus by a NPY Receptor Antagonist: A Site of NPY Action1

Endocrinology ◽

10.1210/endo.140.10.7058 ◽

1999 ◽

Vol 140 (10) ◽

pp. 4494-4500 ◽

Cited By ~ 25

Author(s):

Makoto Yokosuka ◽

Pushpa S. Kalra ◽

Satya P. Kalra

Keyword(s):

Neuropeptide Y ◽

Receptor Antagonist ◽

Paraventricular Nucleus ◽

Npy Receptor ◽

A Site

Download Full-text

(2S,6S)- and (2R,6R)-hydroxynorketamine inhibit the induction of NMDA receptor-dependent LTP at hippocampal CA1 synapses in mice

Brain and Neuroscience Advances ◽

10.1177/2398212820957847 ◽

2020 ◽

Vol 4 ◽

pp. 239821282095784

Author(s):

Heather Kang ◽

Pojeong Park ◽

Muchun Han ◽

Patrick Tidball ◽

John Georgiou ◽

...

Keyword(s):

Synaptic Plasticity ◽

Nmda Receptor ◽

Long Term Potentiation ◽

Aspartate Receptor ◽

Term Potentiation ◽

Hippocampal Ca1 ◽

Mouse Hippocampus ◽

Site Of Action ◽

A Site

The ketamine metabolite (2 R,6 R)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of ( R,S)-ketamine with the (2 S,6 S)- and (2 R,6 R)-isomers of hydroxynorketamine to affect the induction of N-methyl-d-aspartate receptor–dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1–10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2 S,6 S)-hydroxynorketamine. At a concentration of 10 μM, (2 R,6 R)-hydroxynorketamine also inhibited the induction of long-term potentiation. These findings raise the possibility that inhibition of N-methyl-d-aspartate receptor–mediated synaptic plasticity is a site of action of the hydroxynorketamine metabolites with respect to their rapid and long-lasting antidepressant-like effects.

Download Full-text

The field is ever further: In search of the elusive space of fieldwork

Ethnography ◽

10.1177/1466138119898744 ◽

2020 ◽

pp. 146613811989874

Author(s):

Darryl Stellmach

Keyword(s):

Humanitarian Intervention ◽

Narrative Ethnography ◽

Humanitarian Action ◽

Methodological Tool ◽

Site Of Action ◽

And Performance ◽

A Site

This short reflection considers how humanitarian workers conceptualize and practice “the field” as a site of action. Through the use of narrative ethnography, and drawing on comparisons with the practice of academic anthropology, it attempts to draw out disciplinary assumptions that govern how and where humanitarian action is undertaken. It demonstrates how the field is a central imaginary that underpins the principles and performance of both anthropology and humanitarian action. It highlights how the conceptualization of “the field” is itself a methodological tool in the practice of humanitarian intervention.

Download Full-text