Role of nitric oxide in non‐adrenergic, non‐cholinergic inhibitory junction potentials in canine ileocolonic sphincter

Abstract

1 Electrical field stimulation causes neurally-mediated relaxation of the ileocolonic sphincter that is due to activation of non-adrenergic and non-cholinergic (NANC) nerves. Recent studies have suggested that nitric oxide (NO) is the neurotransmitter that mediates relaxation. 2 Using intracellular recording techniques, we have tested whether NANC inhibitory junction potentials (ij.ps) in the canine ileocolonic sphincter are also mediated by NO. 3 Electrical field stimulation elicited excitatory and inhibitory junction potentials: ej.ps were blocked by atropine (10-6 M) and tetrodotoxin (TTX; 10-6 M); ij.ps were also blocked by TTX and partially blocked by apamin (10-6 M). I.j.ps were unaffected by atropine, phentolamine and propranolol (all at 10-6 M). 4 The arginine analogues, L-N0-nitroarginine methyl ester (L-NAME) and N0-monomethyl-L-arginine (L-NMMA), decreased the amplitude of ij.ps and L-arginine, but not D-arginine, partially restored the '.J.ps.5 Ij.ps were also inhibited by oxyhaemoglobin (1%), but not by methaemoglobin. 6 Exogenous NO (1 -7M to 3 x 1 -5M) caused concentration-dependent hyperpolarizations that were similar in amplitude to the NANC nerve-evoked ij.ps. Hyperpolarizations to NO were unaffected by L-NAME, but were blocked by oxyhaemoglobin. 7 Tetrodotoxin, L-NAME and oxyhaemoglobin all caused depolarization of resting membrane potential. 8 The specific guanosine 3':5'-cyclic monophosphate phosphodiesterase inhibitor, M&B 22948, caused hyperpolarization, increased the maximum level of hyperpolarization reached during ij.ps, and increased the duration of ij.ps. 9 These data further support the hypothesis that NANC neurotransmission in the ileocolonic sphincter is mediated by NO or an NO-releasing compound. The data also suggest that tonic release of NO, possibly from spontaneous firing of NANC nerves, may regulate resting membrane potential and tone in this sphincter.

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…suggested that these changes have a myogenic origin, caused by the release of Ca 2ϩ from intracellular stores, acting on Ca 2ϩ -activated chloride channels. In contrast to several other smooth muscle tissues in which NO act as an inhibitory NANC transmitter Thornbury et al, 1991;Ward et al, 1992), the nitrergic inhibitory neurotransmission in the rabbit urethral smooth muscle seemed to be mediated through mechanisms, which do not involve membrane hyperpolarization (Waldeck et al, 1998). This contradicts results reported by Ito and Kimoto (1985), who observed inhibitory junction potentials in some registrations from rabbit urethral smooth muscle.…”

α2‐Adrenoceptor‐mediated modulation of the nitrergic innervation of the canine isolated ileocolonic junction

“…Furthermore, the involvement of other putative NANC neurotransmitters such as adenosine 5'-triphosphate, vasoactive intestinal polypeptide, GABA and 5-HT had been excluded earlier (Boeckxstaens et al, 1990b-e). Recently, electrophysiological evidence was also provided confirming the role of NO in the ileocolonic junction (Ward et al, 1992). This knowledge, together with morphological evidence demonstrating the presence of NO synthase in its myenteric neurones (unpublished observations), make the ileocolonic junction an interesting model to study possible prejunctional regulation of NO release.…”

Effects of nitric oxide (NO) and NO donors on the membrane conductance of circular smooth muscle cells of the guinea‐pig proximal colon

“…In contrast, NOS inhibition reduces both the apamin-sensitive and apamin-resistant components of the i.j.p. recorded in the dog ileocolonic sphincter (Ward et al, 1992c). In addition, many gastrointestinal preparations often display a period of 'rebound' contraction and post-stimulus depolarization (PSD) following the NANC ij.p.…”