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

2008 ◽  
Vol 295 (1) ◽  
pp. R243-R251 ◽  
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.

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

2010 ◽  
Vol 109 (4) ◽  
pp. 1002-1010 ◽  
Author(s):  
Donatella Mutolo ◽  
Fulvia Bongianni ◽  
Elenia Cinelli ◽  
Tito Pantaleo
Keyword(s):  
Receptor Antagonist ◽  
Respiratory Activity ◽  
Neural Substrates ◽  
Cough Reflex ◽  
Ventral Respiratory Group ◽  
Tracheal Pressure ◽  
Site Of Action ◽  
A Site ◽  
Antitussive Agents ◽  
Antitussive Drugs

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.

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

2012 ◽  
Vol 302 (8) ◽  
pp. R976-R983 ◽  
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.

scholarly journals Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

2014 ◽  
Vol 307 (11) ◽  
pp. R1358-R1367 ◽  
Author(s):  
Donatella Mutolo ◽  
Elenia Cinelli ◽  
Fulvia Bongianni ◽  
Tito Pantaleo
Keyword(s):  
Inhibitory Control ◽  
Tracheobronchial Tree ◽  
Nucleus Tractus Solitarii ◽  
Cycle Duration ◽  
Cough Reflex ◽  
Central Processing ◽  
Airway Mucosa ◽  
Galanin Receptors ◽  
Spontaneously Breathing ◽  
Stimulation Of

The caudal nucleus tractus solitarii (NTS) is the main central station of cough-related afferents and a strategic site for the modulation of the cough reflex. The similarities between the characteristics of central processing of nociceptive and cough-related inputs led us to hypothesize that galanin, a neuropeptide implicated in the control of pain, could also be involved in the regulation of the cough reflex at the level of the NTS, where galanin receptors have been found. We investigated the effects of galanin and galnon, a nonpeptide agonist at galanin receptors, on cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30–50 nl) into the caudal NTS of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Galnon antitussive effects on cough responses to the mechanical stimulation of the airway mucosa via a custom-built device were also investigated. Bilateral microinjections of 1 mM galanin markedly decreased cough number, peak abdominal activity, and increased cough-related total cycle duration. Bilateral microinjections of 1 mM galnon induced mild depressant effects on cough, whereas bilateral microinjections of 10 mM galnon caused marked antitussive effects consistent with those produced by galanin. Galnon effects were confirmed by using the cough-inducing device. The results indicate that galanin receptors play a role in the inhibitory control of the cough reflex at the level of the caudal NTS and provide hints for the development of novel antitussive strategies.

Effects of Diphenylether Herbicides on Reactions of Mitochondria and Chloroplasts

Weed Science ◽  
1970 ◽  
Vol 18 (5) ◽  
pp. 636-642 ◽  
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.

scholarly journals Innervation of the pancreas by substance P, enkephalin, vasoactive intestinal polypeptide and gastrin/CCK immunoractive nerves.

1979 ◽  
Vol 27 (9) ◽  
pp. 1283-1284 ◽  
Author(s):  
L I Larsson
Keyword(s):  
Blood Flow ◽  
Insulin Secretion ◽  
Substance P ◽  
Blood Vessels ◽  
Vasoactive Intestinal Polypeptide ◽  
Pancreatic Blood Flow ◽  
Major Site ◽  
Site Of Action ◽  
Immunocytochemical Studies ◽  
Intestinal Polypeptide

Immunocytochemical studies habe shown that many peptides which profoundly affect the endocrine and exocrine functions of the pancreas are localized to neurons. In the cat, such peptidergic nerves appear to innervate ganglia, islets and blood vessels of the pancreas, whereas their contributions to exocrine cells are minor. Our studies suggest that pancreatic ganglia represent one major site of action of the peptides and that, in addition, nerves containing the vasoactive intestinal polypeptide and gastrin/CCK-related peptides profoundly affect pancreatic blood flow and insulin secretion, respectively.

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