- Poster presentation
Substance P and NK1receptor activation within the ventral medullary respiratory network prolongs expiratory time
Respiratory Researchvolume 2, Article number: P3 (2001)
Substance P exerts different effects when applied to the medullary respiratory network. In vivo microinjection of substance P into the ventrolateral medulla prolongs expiratory time and augments tidal volume [1,2] whereas respiratory frequency is enhanced in rhythmic in vitro preparations of immature rat [3,4]. Here, we microinjected substance P and an NK1 receptor agonist (GR73632) into the ventral respiratory group of an arterially perfused, in situ, working heart-brainstem preparation of mature rat. We wished to determine (i) the effects of NK1 receptor activation in the ventral medullary respiratory network of this perfused preparation and (ii), the neuronal mechanism that could account for any changes in respiratory motor outflow.
Unilateral microinjection of substance P (1000 pmol) into the ventral respiratory group prolonged phrenic nerve activity cycle length from 2.0 ± 0.2–4.0 ± 0.7 s (P < 0.01; n = 7 sites). Qualitatively a similar response was observed with GR73632 (100 pmol). At these responsive sites, CP-99,994, an NK1 receptor antagonist, failed to affect respiratory motor output. Recordings from the central end of the vagus nerve indicated both inspiratory and post-inspiratory discharge (ie, stageI expiratory activity) in control. Following a microinjection of substance P, post-inspiratory discharge was both augmented and prolonged. Extracellular recordings were made from 23 respiratory neurones using compound microelectrodes for pressure ejection of drugs. Substance P (10 mM) excited 66% of post-inspiratory neurones raising both the peak firing frequency and total number of action potentials per cycle by 15% and 56% respectively; both effects were prevented by antagonising NK1 receptors.
Our findings indicate that substance P acting on NK1 receptors in the ventral respiratory network promotes a prolongation of expiratory time via an excitatory effect on some post-inspiratory neurones.
Chen Z, Enberg G, Hedner T, Hedner J: Antagonistic effects of somatostatin and substance P on respiratory regulation in the rat ventrolateral medulla oblongata. Brain Res. 1991, 556: 13-21. 10.1016/0006-8993(91)90542-4.
Haxhiu MA, Cherniack NS, van Lunteren E: Central action of tachykinins on activity of expiratory pumping muscles. J Appl Physiol. 1990, 69: 1981-1986.
Gray PA, Rekling JC, Bocchiaro M, Feldman JL: Modulation of respiratory frequency by peptidergic input to rhythmogenic neurons in the preBotzinger complex. Science. 1999, 286: 1566-1568. 10.1126/science.286.5444.1566.
Monteau R, Ptak K, Broquere N, Hilaire G: Tachykinins and central respiratory activity: an in vitro study on the newborn rat. Eur J Pharmacol. 1996, 314: 41-50. 10.1016/S0014-2999(96)00529-8.
Paton JFR: A working heart-brainstem preparation of the mouse. J Neurosci Meth. 1996, 65: 63-68. 10.1016/0165-0270(95)00147-6.
Studies were approved by the Home Office. University of Bristol, Pfizer and British Heart Foundation funded research