AJP - Cell Physiology, Vol 257, Issue 3 C488-C494, Copyright © 1989 by American Physiological Society
Utility of AICAr for metabolic studies is diminished by systemic effects in situ
J. M. Foley, G. R. Adams and R. A. Meyer
Department of Physiology, Michigan State University, East Lansing 48824.
It has been reported that intraperitoneal infusion of
5-amino-4-imidazolecarboxamide riboside (AICAr) inhibits the purine
nucleotide cycle, resulting in rapid fatigue of isometric twitch force
during stimulation of rat muscle. In this study, peak isometric twitch
force was recorded from gastrocnemius muscles of pentobarbital-anesthetized
rats stimulated in situ at 0.75 Hz after intraperitoneal infusion of
9ml/100 g body wt of 250 mM AICAr or isotonic saline. Excluding the two
AICAr-infused rats that died during infusion or stimulation, there was no
difference in twitch force between groups, although mean arterial pressure
in the AICAr group declined to values 20 Torr below those of the control
group during drug infusion. High-resolution 1H nuclear magnetic resonance
(NMR) spectroscopy of extracts verified the presence of AICAr and AICA
ribotide (AICAR) in muscles of experimental animals. In a second study in
which rats were mounted head down in an NMR spectrometer, AICAr infusion
resulted in decreased mean arterial pressure and impairment of
phosphocreatine recovery after stimulation but no significant difference in
twitch force during stimulation. These results demonstrate that AICAr
infusion has systemic effects and that the previously reported decline in
muscle force with AICAr infusion may not be attributable to purine
nucleotide cycle inhibition.
