Tachykinins and central respiratory activity: an in vitro study on the newborn rat

The newborn rat brainstem-spinal cord preparation was used to study the effects of tachykinins on the activity of the respiratory rhythm generator in vitro and to characterize the receptors involve. Substance P and tachykinin NK1 and NK3 receptor agonists induced a concentration-dependent increase in the respiratory frequency (10(-9)-10(-7) M), whereas the respiratory frequency was only slightly affected by the tachykinin NK2 receptor agonist. Pre-treatments with tachykinin NK1 receptor antagonists (SR140333, (S)1-¿2-[3-(3.4-dichlorophenyl) -1-(3-isopropoxyphenylacetyl)piperidin-n-3-yl]ethyl¿-4-ph eny l-1-azoniabicyclo [2,2,2]octane chloride; GR82334, pGlu-Ala- Asp-Pro-Asn-Lys-Phe-Tyr-(S-S)Pro-Leu(spiro-gamma-lactam)-Trp-NH2) reduced the substance P-induced increases in the respiratory frequency but the tachykinin NK2 receptor antagonist (SR48968, ((S)-N-methyl-N-[4-4-acetylamino-4-phenylpiperidine)-2-(3,4-dichlorop hen yl) butyl]benzamide); MEN 10376, Asp-Tyr-D-Trp-Val-D-Trp-Lys-NH2) had no effect; the increase in the respiratory frequency induced by the tachykinin NK3 receptor agonist was not affected by a pre-treatment with tachykinin NK1 and NK2 receptor antagonists. These result indicate that tachykinin NK1 and NK3 receptors may be involved in the control of the respiratory frequency.