NITRERGIC STIMULATION DOES NOT INHIBIT CARBACHOL-INDUCED INOSITOL PHOSPHATE GENERATION IN THE RAT ANOCOCCYGEUS

Carbachol (50 mu M) produced a rapid, transient increase in inositol-1 ,4,5-trisphosphate (IP3) levels in the rat anococcygeus; the peak incr ease observed at 10 s (3-fold above controls) was greatly reduced in t he presence of atropine (100 nM), but was unaffected by nitrergic stim ulation (10 Hz), sodium nitroprusside (10 mu M) or 8-Br-cyclic GMP (20 0 mu M). Following loading of muscles with [H-3]myo-inositol, subseque nt exposure to carbachol for 30 min resulted in a 6-fold increase in t he accumulation of [H-3]inositol-1-monophosphate; again, this action o f carbachol was greatly attenuated by atropine, but unaffected by nitr ergic stimulation, sodium nitroprusside or 8-Br-cyclic GMP. It is conc luded that inhibition of agonist-induced generation of inositol phosph ates cannot explain the ability of nitrergic activation to relax (by 5 4%-62%) carbachol-induced tone in this tissue.