Article date: August 1996
By: Katalina Hebeiß, Heinz Kilbinger, in Volume 118, Issue 8, pages 2073-2078
The effects of the nitric oxide (NO) donors, 3‐morpholino‐sydnonimine (SIN‐1), S‐nitroso‐N‐acetylpenicillamine (SNAP) and sodium nitroprusside on basal and electrically evoked release of [3H]‐acetylcholine were studied in myenteric plexus longitudinal muscle preparations of the guinea‐pig small intestine preincubated with [3H]‐choline.
The NO donors concentration‐dependently increased basal release of [3H]‐acetylcholine. The increase in release was calcium‐dependent and was prevented in the presence of tetrodotoxin. Superoxide dismutase (150 u ml−1) potentiated the effect of SIN‐1. The selective inhibitor of soluble guanylyl cyclase, 1H‐[1,2,4]oxadiazolo[4,3‐α]quinoxalin‐1‐one (ODQ, 0.01‐1 μm), antagonized the facilitatory effect of SNAP. 8‐Bromo cyclic GMP and the cyclic GMP‐specific phosphodiesterase inhibitor, zaprinast (both 0.1‐1 mM), also enhanced basal [3H]‐acetylcholine release. The effect of 10 μm SNAP was significantly enhanced in the presence of zaprinast.
The NO donors concentration‐dependently inhibited the electrically evoked release of [3H]‐acetylcholine, whereas 8‐bromo cyclic GMP and zaprinast enhanced the evoked release. The inhibition of acetylcholine release by SNAP was not affected by ODQ (0.01‐1 μm).
It is concluded that NO stimulates basal acetylcholine release from myenteric neurones through activation of guanylyl cyclase. In addition, NO inhibits the depolarization evoked release of acetylcholine by a presynaptic mechanism unrelated to cyclic GMP. The data imply that NO is not only an inhibitory transmitter to intestinal smooth muscles but also a modulator of cholinergic neurotransmission in the myenteric plexus.
The effects of the nitric oxide (NO) donors, 3‐morpholino‐sydnonimine (SIN‐1), S‐nitroso‐N‐acetylpenicillamine (SNAP) and sodium nitroprusside on basal and electrically evoked release of [3H]‐acetylcholine were studied in myenteric plexus longitudinal muscle preparations of the guinea‐pig small intestine preincubated with [3H]‐choline.
The NO donors concentration‐dependently increased basal release of [3H]‐acetylcholine. The increase in release was calcium‐dependent and was prevented in the presence of tetrodotoxin. Superoxide dismutase (150 u ml−1) potentiated the effect of SIN‐1. The selective inhibitor of soluble guanylyl cyclase, 1H‐[1,2,4]oxadiazolo[4,3‐α]quinoxalin‐1‐one (ODQ, 0.01‐1 μm), antagonized the facilitatory effect of SNAP. 8‐Bromo cyclic GMP and the cyclic GMP‐specific phosphodiesterase inhibitor, zaprinast (both 0.1‐1 mM), also enhanced basal [3H]‐acetylcholine release. The effect of 10 μm SNAP was significantly enhanced in the presence of zaprinast.
The NO donors concentration‐dependently inhibited the electrically evoked release of [3H]‐acetylcholine, whereas 8‐bromo cyclic GMP and zaprinast enhanced the evoked release. The inhibition of acetylcholine release by SNAP was not affected by ODQ (0.01‐1 μm).
It is concluded that NO stimulates basal acetylcholine release from myenteric neurones through activation of guanylyl cyclase. In addition, NO inhibits the depolarization evoked release of acetylcholine by a presynaptic mechanism unrelated to cyclic GMP. The data imply that NO is not only an inhibitory transmitter to intestinal smooth muscles but also a modulator of cholinergic neurotransmission in the myenteric plexus.
DOI: 10.1111/j.1476-5381.1996.tb15646.x
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