Cardiorespiratory effects of inositol hexakisphosphate following microinjections into the nucleus tractus solitarii

Abstract

Microinjections of inositol hexakisphosphate (IP6), a metabolite of inositol recently found to occur in high concentrations in the brainstem, were made into the caudal portion of the nucleus tractus solitarii (NTS) of spontaneously breathing rats and cardiorespiratory parameters recorded for a 30 min test period. Microinjections of IP6, in the dose range of 100-500 pmol/rat, produced significant dose-related reductions in mean arterial blood pressure and respiratory rate. The onset for hypotensive action and respiratory depression following microinjections of IP6 was very rapid and a transient apnea could be elicited at the higher doses. Moreover, the sodium and calcium salts of IP6 were relatively equipotent in depressing cardiorespiratory parameters, with the exception of heart rate wherein the sodium salt elicited a much more pronounced bradycardia. These results confirm and extend the findings of a previous study suggesting that IP6 and closely related metabolites may act on extracellular receptors. Taken together, these data provide further support to the notion that inositol lipid signalling pathways may generate both intracellular and extracellular signals in the brain.