TY - JOUR
T1 - Role of nitric oxide- and vasoactive intestinal polypeptide-containing neurones in human gastric fundus strip relaxations
AU - Tonini, M.
AU - De Giorgio, R.
AU - De Ponti, F.
AU - Sternini, C.
AU - Spelta, V.
AU - Dionigi, P.
AU - Barbara, G.
AU - Stanghellini, V.
AU - Corinaldesi, R.
PY - 2000
Y1 - 2000
N2 - 1. The morphological pattern and motor correlates of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) innervation in the human isolated gastric fundus was explored. 2. 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 these positive for VIP-IR. The majority of myenteric neurones containing VIP coexpressed NADPH-diaphorase. 3. Electrical stimulation of fundus strips caused frequency-dependent NANC relaxations. N(G)-nitro-L-arginine (L-NOARG: 300 μM) 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 nM) desensitization at all frequencies. 4. Relaxations to graded low mechanical distension (≤ l g) were insensitive to tetrodotoxin (TTX: 1 μM) and L-NOARG (300 μM), while those to higher distensions (2 g) were slightly inhibited by both agents to the same extent (~ 25). 5. 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.
AB - 1. The morphological pattern and motor correlates of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) innervation in the human isolated gastric fundus was explored. 2. 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 these positive for VIP-IR. The majority of myenteric neurones containing VIP coexpressed NADPH-diaphorase. 3. Electrical stimulation of fundus strips caused frequency-dependent NANC relaxations. N(G)-nitro-L-arginine (L-NOARG: 300 μM) 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 nM) desensitization at all frequencies. 4. Relaxations to graded low mechanical distension (≤ l g) were insensitive to tetrodotoxin (TTX: 1 μM) and L-NOARG (300 μM), while those to higher distensions (2 g) were slightly inhibited by both agents to the same extent (~ 25). 5. 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.
KW - Electrically-induced relaxations
KW - Human gastric fundus
KW - Mechanically-induced relaxations
KW - NADPH-diaphorase histochemistry
KW - NANC inhibitory nerves
KW - VIP and NOS-immunohistochemistry
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M3 - Article
C2 - 10694197
AN - SCOPUS:0033980815
SN - 0007-1188
VL - 129
SP - 12
EP - 20
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 1
ER -