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Role of nitric oxide‐ and vasoactive intestinal polypeptide‐containing neurones in human gastric fundus strip relaxations
Author(s) -
Tonini M,
De Giorgio R,
De Ponti F,
Sternini C,
Spelta V,
Dionigi P,
Barbara G,
Stanghellini V,
Corinaldesi R
Publication year - 2000
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 - 10.1038/sj.bjp.0702977
Subject(s) - vasoactive intestinal peptide , medicine , endocrinology , myenteric plexus , nitric oxide synthase , nitroarginine , nitric oxide , stimulation , tetrodotoxin , enteric nervous system , chemistry , biology , neuropeptide , immunohistochemistry , receptor
The morphological pattern and motor correlates of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) innervation in the human isolated gastric fundus was explored. By using the nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)‐diaphorase and specific rabbit polyclonal NO‐synthase (NOS) and VIP antisera, NOS‐ and VIP‐containing varicose nerve fibres were identified throughout the muscle layer or wrapping ganglion cell bodies of the myenteric plexus. NOS‐immunoreactive (IR) neural cell bodies were more abundant than those positive for VIP‐IR. The majority of myenteric neurones containing VIP coexpressed NADPH‐diaphorase. Electrical stimulation of fundus strips caused frequency‐dependent NANC relaxations. N G ‐nitro‐ L ‐arginine ( L ‐NOARG: 300 μ M ) enhanced the basal tone, abolished relaxations to 0.3–3 Hz (5 s) and those to 1 Hz (5 min), markedly reduced (∼50%) those elicited by 10–50 Hz, and unmasked or potentiated excitatory cholinergic responses at frequencies 1 Hz. L ‐NOARG‐resistant relaxations were virtually abolished by VIP (100 n M ) desensitization at all frequencies. Relaxations to graded low mechanical distension (1 g) were insensitive to tetrodotoxin (TTX: 1 μ M ) and L ‐NOARG (300 μ M ), while those to higher distensions (2 g) were slightly inhibited by both agents to the same extent (∼25%). In the human gastric fundus, NOS‐ and VIP immunoreactivities are colocalized in the majority of myenteric neurones. NO and VIP mediate electrically evoked relaxations: low frequency stimulation, irrespective of the duration, caused NO release only, whereas shortlasting stimulation at high frequencies induced NO and VIP release. Relaxations to graded mechanical distension were mostly due to passive viscoelastic properties, with a slight NO‐mediated neurogenic component at 2 g distension. The difference between NO and VIP release suggests that in human fundus accommodation is initiated by NO.British Journal of Pharmacology (2000) 129 , 12–20; doi: 10.1038/sj.bjp.0702977