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Modulation of the cough reflex by GABA(A) receptors in the caudal ventral respiratory group of the rabbit.

Cinelli E, Bongianni F, Pantaleo T, Mutolo D - Front Physiol (2012)

Bottom Line: Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E).On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E).However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Fisiologiche, Università degli Studi di Firenze Firenze, Italy.

ABSTRACT
We have previously shown that the caudal ventral respiratory group (cVRG) is a possible site of action of some antitussive drugs and plays a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. In addition, it has been reported that medullary expiratory neurons of the cVRG are subject to potent GABAergic gain modulation. This study was devoted to investigate the role of cVRG GABA(A) receptors in the control of baseline respiratory activity and cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. To this purpose, bilateral microinjections (30-50 nl) of bicuculline or muscimol were performed into the cVRG of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E). Cough responses were potentiated mainly owing to increases in the cough number. The recovery was observed within ~2 h. On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E). In addition, cough responses were progressively reduced and completely suppressed within ~20 min. Partial recovery of cough responses was achieved after ~3 h or within ~5 min following bicuculline microinjections at the same locations. The sneeze reflex induced by mechanical stimulation of the nasal mucosa persisted following bicuculline and muscimol microinjections. However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol. The results provide evidence that a potent GABA(A)-mediated inhibitory modulation is exerted at the level of the cVRG not only on respiratory activity, but also on cough and sneeze reflex responses.

No MeSH data available.


Related in: MedlinePlus

Depressant effects on the cough reflex and on the sneeze reflex ~20 min following bilateral microinjections of muscimol into the cVRG of one anesthetized spontaneously breathing rabbit. The recovery of reflex responses ~5 min after 1 mM bicuculline microinjections is reported. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.
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Figure 3: Depressant effects on the cough reflex and on the sneeze reflex ~20 min following bilateral microinjections of muscimol into the cVRG of one anesthetized spontaneously breathing rabbit. The recovery of reflex responses ~5 min after 1 mM bicuculline microinjections is reported. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.

Mentions: Bilateral microinjections (n = 5) of 0.3 mM muscimol (30–50 nl; 9–15 pmol) into the cVRG decreased respiratory frequency (from 52.4 ± 2.3 to 38.5 ± 2.7 breaths min−1; P < 0.005) due to increases in TE and abolished abdominal activity (Table 1). Changes in respiratory activity developed progressively, reached a maximum within ~10 min and displayed partial recovery after ~3 h. Arterial blood pressure did not change (Table 1). End-tidal CO2 partial pressure increased from 26.80 ± 0.77 to 33.22 ± 0.66 mmHg (P < 0.05). Cough responses induced by both mechanical and chemical stimulation of the tracheobronchial tree were progressively reduced to barely appreciable single coughs or completely suppressed within ~20 min following muscimol microinjections (Table 2 and Figure 3). Correspondingly, sneeze reflex responses displayed progressive decreases until the expiratory thrusts were hardly visible or abolished, while the preparatory inspiratory bursts persisted without significant changes in amplitude (Table 3 and Figure 3). Cough and sneeze responses recovered, although not completely, after ~3 h (n = 2) or within ~5 min following 1 mM bicuculline microinjections at the same cVRG locations (n = 3).


Modulation of the cough reflex by GABA(A) receptors in the caudal ventral respiratory group of the rabbit.

Cinelli E, Bongianni F, Pantaleo T, Mutolo D - Front Physiol (2012)

Depressant effects on the cough reflex and on the sneeze reflex ~20 min following bilateral microinjections of muscimol into the cVRG of one anesthetized spontaneously breathing rabbit. The recovery of reflex responses ~5 min after 1 mM bicuculline microinjections is reported. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475209&req=5

Figure 3: Depressant effects on the cough reflex and on the sneeze reflex ~20 min following bilateral microinjections of muscimol into the cVRG of one anesthetized spontaneously breathing rabbit. The recovery of reflex responses ~5 min after 1 mM bicuculline microinjections is reported. Stimulation periods marked by filled bars. Phr IN, phrenic integrated neurogram; Phr N, phrenic neurogram; Abd IEMG, abdominal integrated electromyographic activity; Abd EMG, abdominal electromyographic activity.
Mentions: Bilateral microinjections (n = 5) of 0.3 mM muscimol (30–50 nl; 9–15 pmol) into the cVRG decreased respiratory frequency (from 52.4 ± 2.3 to 38.5 ± 2.7 breaths min−1; P < 0.005) due to increases in TE and abolished abdominal activity (Table 1). Changes in respiratory activity developed progressively, reached a maximum within ~10 min and displayed partial recovery after ~3 h. Arterial blood pressure did not change (Table 1). End-tidal CO2 partial pressure increased from 26.80 ± 0.77 to 33.22 ± 0.66 mmHg (P < 0.05). Cough responses induced by both mechanical and chemical stimulation of the tracheobronchial tree were progressively reduced to barely appreciable single coughs or completely suppressed within ~20 min following muscimol microinjections (Table 2 and Figure 3). Correspondingly, sneeze reflex responses displayed progressive decreases until the expiratory thrusts were hardly visible or abolished, while the preparatory inspiratory bursts persisted without significant changes in amplitude (Table 3 and Figure 3). Cough and sneeze responses recovered, although not completely, after ~3 h (n = 2) or within ~5 min following 1 mM bicuculline microinjections at the same cVRG locations (n = 3).

Bottom Line: Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E).On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E).However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Fisiologiche, Università degli Studi di Firenze Firenze, Italy.

ABSTRACT
We have previously shown that the caudal ventral respiratory group (cVRG) is a possible site of action of some antitussive drugs and plays a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. In addition, it has been reported that medullary expiratory neurons of the cVRG are subject to potent GABAergic gain modulation. This study was devoted to investigate the role of cVRG GABA(A) receptors in the control of baseline respiratory activity and cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. To this purpose, bilateral microinjections (30-50 nl) of bicuculline or muscimol were performed into the cVRG of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Bicuculline (1 mM) increased peak abdominal activity and respiratory frequency due to decreases in T(E). Cough responses were potentiated mainly owing to increases in the cough number. The recovery was observed within ~2 h. On the contrary, muscimol (0.3 mM) abolished abdominal activity and decreased respiratory frequency due to increases in T(E). In addition, cough responses were progressively reduced and completely suppressed within ~20 min. Partial recovery of cough responses was achieved after ~3 h or within ~5 min following bicuculline microinjections at the same locations. The sneeze reflex induced by mechanical stimulation of the nasal mucosa persisted following bicuculline and muscimol microinjections. However, the number and intensity of expiratory thrusts were enhanced by bicuculline and suppressed by muscimol. The results provide evidence that a potent GABA(A)-mediated inhibitory modulation is exerted at the level of the cVRG not only on respiratory activity, but also on cough and sneeze reflex responses.

No MeSH data available.


Related in: MedlinePlus