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Modulation of cholinergic and substance P‐like neurotransmission by nitric oxide in the guinea‐pig ileum
Author(s) -
Wiklund Claes U.,
Olgart Caroline,
Wiklund N. Peter,
Gustafsson Lars E.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13888.x
Subject(s) - neurotransmission , acetylcholine , nitric oxide synthase , endocrinology , myenteric plexus , cholinergic , medicine , neurotransmitter , substance p , chemistry , inhibitory postsynaptic potential , biology , receptor , neuropeptide , nitric oxide , central nervous system , immunohistochemistry
1 The role of endogenous nitric oxide (NO) as a modulator of enteric neurotransmission was investigated in longitudinal muscle myenteric plexus (LMMP) preparations of guinea‐pig isolated ileum. 2 In tissues previously incubated with [ 3 H]‐choline, exogenous NO inhibited electrically‐evoked [ 3 H]‐choline overflow as well as responses to exogenous agonists, indicating that NO has the potential of neuromodulation both pre‐ and postjunctionally. 3 A series of NO synthase inhibitors enhanced contractile responses to nerve stimulation indicating inhibitory neuromodulation by endogenous NO. 4 The potency order of the NO synthase inhibitors and their consistent effects after dexamethasone, on responses to nerve stimulation, indicate action on a constitutive NO synthase. 5 Responses enhanced by NO synthase inhibitors were inhibited by the substance P receptor antagonist, spantide, suggesting a neuromodulatory influence on substance P‐like neurotransmission by the endogenous NO. 6 NO synthase inhibition did not modify contractile responses to application of acetylcholine or substance P, or [ 3 H]‐choline overflow, indicating that endogenous NO mainly has a prejunctional inhibitory action on substance P‐like neurotransmission. Nor did it modify responses to direct electrical muscle stimulation in the presence of tetrodotoxin. This suggests a prejunctional enhancing effect by NO synthesis inhibition. 7 Evidence for endogenous NO modulation of acetylcholine release was obtained when NO synthase inhibition modified atropine‐sensitive, nerve‐mediated contractile responses. However, [ 3 H]‐choline overflow was unaltered by NO synthase inhibition. 8 NO synthase inhibition did not modify responses to inhibitory neurotransmission. 9 The findings suggest that endogenous NO inhibits substance P‐like motor neurotransmission, probably via prejunctional mechanisms. Cholinergic transmission may also be reduced by endogenous NO, acting prejunctionally.