Utility of AICAr for metabolic studies is diminished by systemic effects in situ

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.