Central respiratory and cardiovascular effects in the rat of some putative neurotransmitter amino acids.

Abstract

Respiratory performance was studied in halothane anesthetized rats after intracerebroventricular (i.c.v.) injection of beta-alanine, taurine or glycine (0.01--1 mg). The amino acids induced a marked decrease in both respiratory frequency (f) and tidal volume (VT), which was immediate and longlasting. The respiratory depressant action of glycine could readily be reversed by strychnine, a glycine antagonist. Measurement of respiratory time intervals, inspiratory time (TI), expiratory time (TE) and total cycle duration (TTOT), after administration of the putative neurotransmitter amino acids revealed that the effects on f were due to prolongation of the duration of expiration. The duration of inspiration was principally unaltered, but mean inspiratory flow (VT/TI) and respiratory timing (TI/TTOT) decreased. In experiments employing the occluded breath technique, P0.1 was reduced in the same magnitude as the mean inspiratory flow (VT/TI). The results also showed a change in central (bulbopontine) setting for TE, while the setting to TI was unaltered. An inert amino acid, valine, which was administered i.c.v. in the same doses, had no effects on respiratory parameters. Apart from the effects on basal ventilation of beta-alanine, taurine and glycine, the CO2 induced respiratory response was blunted. These three amino acids also depressed heart rate and mean arterial pressure. Although relatively high doses were used to induce the respiratory effects, it may be hypothetised that the putative neurotransmitters beta-alanine, taurine and glycine may have a physiological role in the central regulation of breathing.