In vivo release of glutamate in nucleus tractus solitarii of the rat during hypoxia.

Abstract

1. An attempt has been made to test the hypothesis that, in the caudal part of nucleus tractus solitarii (NTS) where carotid sinus nerve (CSN) The carotid body is the major peripheral chemoreceptor for hypoxia in humans and other animals, and it plays an important role in augmenting ventilation during hypoxia (Martin-Body, Robson & Sinclair, 1986). In the rat, chemoreceptor afferents from the carotid body travel along the carotid sinus nerve (CSN) and terminate mainly in the caudal nucleus tractus solitarii (NTS; Lipski, McAllen & Spyer, 1977;Donoghue, Felder, Jordan & Spyer, 1984;Housley & Sinclair, 1988). Several neurotransmitters have been found in NTS (Cherniack, Prabhakar, Haxhiu & Runold, 1991). Among them, substance P (Prabhakar, Runold, Yamamoto, Lagercrantz & Euler, 1984;Henry & Sessle, 1985;Lindefors, Yamamoto, Pantaleo, Lagercrantz, Brodin & Ungerstedt, 1986), dopamine (Goiny, Lagercrantz, Srinivasan, Ungerstedt & Yamamoto, 1991) and L-glutamate (Glut; Kazemi, Chiang & Hoop, 1989) are considered to mediate chemoreceptor inputs to NTS. However, which neurotransmitter is released from the CSN in response to peripheral chemoreceptor activation and to what extent it is involved in regulation of respiration has not been determined.In the present study we used unanaesthetized, freely moving rats in which ventilation and in vivo release of Glut in the caudal NTS by microdialysis were measured during peripheral chemoreceptor stimulation by hypoxic hypoxia or doxapram (Dox) infusion in sham-operated and peripherally chemodenervated (carotid body denervated; CBD) rats. Moreover, the effects on ventilation of a local injection of Glut and during hypoxia, of pretreatment with the NMDA-type receptor antagonist MK-801 or the ionotropic receptor antagonist kynurenate into the caudal NTS (Housley & Sinclair, 1988) were investigated. MS 2462, pp. 55-65 55

NMDA receptor-mediated modulation of ventilation in obese Zucker rats

“…In the present study, the ventilatory response to hypoxia noted at a dose of 10 mgakg DM in lean Z rats was similar to responses obtained with other NMDA receptor antagonists in piglets, 11 in dogs 12 and in rats. 13,24 Resting ventilation In the present study, baseline (saline) ventilatory and metabolic variables (Table 1) for both lean and obese rats were within the range of previously published values. 5,18 The primary purpose of the current study, however, was to assess the role of NMDA receptors in modulating ventilation.…”

“…12,13,24,27 For the current study, however, we selected dextromethorphan (DM) over MK-801 because preliminary studies in our lab demonstrated that low doses of MK-801 (0.1 ± 0.5 mgakg, i.p.) produced restlessness and hyperlocomotion in Z rats, while higher doses of MK-801 (1 ± 5 mgakg, i.p.)…”

“…The afferent inputs from carotid sinus nerve project to the glutamatergic synapses in the nucleus tractus solitarius (NTS), which leads to release of glutamate centrally. 13 The increased glutamate increases the activity of NMDA and non-NMDA receptors in brainstem respiratory motor neurons, thus increasing the level of ventilation. 13,14,24 Indeed, glutamate levels are elevated in the NTS and the medulla during brief hypoxic challenges.…”

“…13 The increased glutamate increases the activity of NMDA and non-NMDA receptors in brainstem respiratory motor neurons, thus increasing the level of ventilation. 13,14,24 Indeed, glutamate levels are elevated in the NTS and the medulla during brief hypoxic challenges. 14,15,27 Therefore, the altered pattern of ventilatory response to hypoxia in obese Z rats is suggestive of an altered NMDA receptor mediated mechanism.…”

Glutamatergic neurotransmission modulates hypoxia-induced hyperventilation but not anapyrexia

“…It is known that hyperventilation induced by hypoxia results primarily from the activation of peripheral chemoreceptors located in the aortic and carotid bodies and the subsequent processing of information by the central nervous system (CNS; 12). Mizusawa et al (13) demonstrated that afferent nerve fibers carrying peripheral chemoreceptor impulses to the CNS cause release of L-glutamate during hypoxia. Accordingly, inhibition of L-glutamate receptors nearly abolishes the hyperventilatory response to hypoxia (3,13-17, present data).…”