Nitrergic stimulation does not inhibit carbachol-induced inositol phosphate generation in the rat anococcygeus.
Carbachol (50 microM) produced a rapid, transient increase in inositol-1,4,5-trisphosphate (IP3) levels in the rat anococcygeus; the peak increase observed at 10 s (3-fold above controls) was greatly reduced in the presence of atropine (100 nM), but was unaffected by nitrergic stimulation (10 Hz), sodium nitroprusside (10 microM) or 8-Br-cyclic GMP (200 microM). Following loading of muscles with [3H]myo-inositol, subsequent exposure to carbachol for 30 min resulted in a 6-fold increase in the accumulation of [3H]inositol-1-monophosphate; again, this action of carbachol was greatly attenuated by atropine, but unaffected by nitrergic stimulation, sodium nitroprusside or 8-Br-cyclic GMP. It is concluded that inhibition of agonist-induced generation of inositol phosphates cannot explain the ability of nitrergic activation to relax (by 54-62%) carbachol-induced tone in this tissue.
Gibson
A
A
Biomedical Sciences Division, King's College, London, UK.
Brave
S R
SR
McFadzean
I
I
Mirzazadeh
S
S
Tucker
J F
JF
Wayman
C
C
D001003:Anal Canal; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D007295:Inositol Phosphates; C002647:inositol 1-phosphate; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D007294:Inositol; D001285:Atropine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D006152:Cyclic GMP