5-HT3 receptor-dependent modulation of respiratory burst frequency, regularity, and episodicity in isolated adult turtle brainstems

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706, USA.
Respiratory Physiology & Neurobiology (Impact Factor: 1.97). 06/2010; 172(1-2):42-52. DOI: 10.1016/j.resp.2010.04.008
Source: PubMed


To determine the role of central serotonin 5-HT(3) receptors in respiratory motor control, respiratory motor bursts were recorded from hypoglossal (XII) nerve rootlets on isolated adult turtle brainstems during bath-application of 5-HT(3) receptor agonists and antagonists. mCPBG and PBG (5-HT(3) receptor agonists) acutely increased XII burst frequency and regularity, and decreased bursts/episode. Tropisetron and MDL72222 (5-HT(3) antagonists) increased bursts/episode, suggesting endogenous 5-HT(3) receptor activation modulates burst timing in vitro. Tropisetron blocked all mCPBG effects, and the PBG-induced reduction in bursts/episode. Tropisetron application following mCPBG application did not reverse the long-lasting (2h) mCPBG-induced decrease in bursts/episode. We conclude that endogenous 5-HT(3) receptor activation regulates respiratory frequency, regularity, and episodicity in turtles and may induce a form of respiratory plasticity with the long-lasting changes in respiratory regularity.

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Available from: Julia R Wilkerson, Mar 15, 2015
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    • "Excitation of Post-I-cells may enhance episode termination and transform episodic breathing into singlet breathing. In isolated turtle brainstems , bath-applied 5HT 3 receptor agonist drugs increase singlet breathing while 5HT 3 receptor antagonist drugs increase episodic breathing (Bartman et al., 2010). Similarly, hypoxia-induced singlet breathing in intact turtles is abolished by pretreatment with 5HT 3 receptor antagonist drugs (S.M. Johnson, A.R. Krisp, M.E. "
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    ABSTRACT: It is not known whether respiratory neurons with intrinsic bursting properties exist within ectothermic vertebrate respiratory control systems. Thus, isolated adult turtle brainstems spontaneously producing respiratory motor output were used to identify and classify respiratory neurons based on their firing pattern relative to hypoglossal (XII) nerve activity. Most respiratory neurons (183/212) had peak activity during the expiratory phase, while inspiratory, post-inspiratory, and novel pre-expiratory neurons were less common. During synaptic blockade conditions, ∼10% of respiratory neurons fired bursts of action potentials, with post-inspiratory cells (6/9) having the highest percentage of intrinsic burst properties. Most intrinsically bursting respiratory neurons were clustered at the level of the vagus (X) nerve root. Synaptic inhibition blockade caused seizure-like activity throughout the turtle brainstem, which shows that the turtle respiratory control system is not transformed into a network driven by intrinsically bursting respiratory neurons. We hypothesize that intrinsically bursting respiratory neurons are evolutionarily conserved and represent a potential rhythmogenic mechanism contributing to respiration in adult turtles.
    Full-text · Article · Nov 2014 · Respiratory Physiology & Neurobiology
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    • "4–5; Bartman et al., 2010). The respiratory rhythm within respiratory events in turtle brainstems appears to be regulated by a 5-HT 3 -dependent mechanism because 5-HT 3 receptor activation and blockade changes bursts/respiratory event (Bartman et al., 2010). The phenylephrine-induced decrease in bursts/respiratory event was not blocked by coapplication of α 1 and 5-HT 3 receptor antagonist drugs (Fig. 6A), suggesting that phenylephrine acts by an unknown mechanism (see discussion above). "
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    ABSTRACT: The effects of brainstem α(1) adrenergic receptor activation on respiratory control in reptiles are poorly understood. Isolated adult turtle brainstems were exposed to phenylephrine (α(1) adrenergic agonist) and respiratory motor bursts were recorded on hypoglossal nerves. Phenylephrine acutely increased burst frequency, amplitude (low concentrations only), and regularity of the time interval between the start of respiratory events (single or clustered bursts), and decreased bursts/respiratory event. Burst frequency and timing changes persisted during a 2.0 h washout. Acute increases in burst frequency and amplitude were blocked by prazosin (α(1) adrenergic antagonist). Pretreatment with prazosin and tropisetron (5-HT(3) antagonist) blocked the increase in respiratory event regularity, but did not alter the decrease in bursts/respiratory event. Intermittent phenylephrine application (4 × 5.0 min separated by 20 min) did not produce long-lasting changes in burst frequency and amplitude, bursts/respiratory event, or respiratory event regularity. Thus, sustained α(1) adrenergic receptor activation in turtle brainstems produces acute and long-lasting changes in respiratory burst frequency and pattern.
    Preview · Article · Mar 2012 · Respiratory Physiology & Neurobiology
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    • "Serotonergic neurons in the brainstem project to various sites in the central nervous system and exert powerful neuromodulatory influences on the motor system, such as respiratory control (20,21). However, serotonin receptor activation can produce both excitatory and inhibitory effects on respiratory control, which appears to be related to experimental preparation, developmental stage, animal species, and route of drug administration (22). "
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    ABSTRACT: The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8/per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg-1·day-1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7%), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9%, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.
    Full-text · Article · Nov 2011 · Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.]
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