Role of nitric oxide‐ and vasoactive intestinal polypeptide‐containing neurones in human gastric fundus strip relaxations

Abstract

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 speci®c rabbit polyclonal NO-synthase (NOS) and VIP antisera, NOS-and VIP-containing varicose nerve ®bres were identi®ed 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 NADPHdiaphorase. 3 Electrical stimulation of fundus strips caused frequency-dependent NANC relaxations. N G -nitro-L-arginine (L-NOARG: 300 mM) 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 51 Hz. L-NOARG-resistant relaxations were virtually abolished by VIP (100 nM) desensitization at all frequencies. 4 Relaxations to graded low mechanical distension (41 g) were insensitive to tetrodotoxin (TTX: 1 mM) and L-NOARG (300 mM), 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 di erence between NO and VIP release suggests that in human fundus accommodation is initiated by NO.

Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine?

“…Peptide mediators such as substance P, pituitary adenylate cyclase-activating polypeptide, and VIP (10,25,29,30,51) are released at higher frequencies of electrical field stimulation (EFS) of enteric and autonomic nerves. We chose EFS stimulus parameters (50 V/cm, 0.5 ms, 5 pps) that minimize the release of peptide mediators.…”

Relaxation Patterns of Human Gastric Corporal Smooth Muscle by Cyclic Nucleotides Producing Agents

“…Most mechanical and electrical properties in human GI tract have been investigated using electrogastrograph (EGG) and ultrasonography (Hocke et al, 2009;Matsumoto et al, 2009), although several in vitro GI motility studies have been reported (Tonini et al, 2000;Farrelly et al, 2003;Severi et al, 2006;Wang et al, 2007). In this in vitro study, we first characterized mechanical properties.…”

“…Isoproterenol (ISO) and nitric oxide (NO) produce membrane hyperpolarization, decrease slow wave, and then inhibit contraction via activation of adenylate and guanylate cyclase in GI tract (Ozaki et al, 1992;Jin et al, 1993;Smith et al, 1993;Severi et al, 2006). Especially, NO is recognized as a neurotransmitter of nonadrenergic non-cholinergic (NANC) nerves in the myenteric plexus throughout the GI tract and is responsible for gastric receptive relaxation (Ozaki et al, 1992;Jin et al, 1993;Smith et al, 1993;Tonini et al, 2000). In addition, sodium nitroprusside (SNP), known NO-releasing compound, is reported to stimulate guanylate cyclase and then increase intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels, while forskolin (FSK) to stimulate adenylate cyclase and then adenosine 3',5'-cyclic monophosphate (cAMP) levels in many smooth muscles, including GI tract (Katsuki et al, 1977;Huizinga et al, 1991;Ozaki et al, 1992;Jin et al, 1993;Smith et al, 1993;Severi et al, 2006).…”

Mechanisms responsible for neuromuscular relaxation in the gastrointestinal tract

“…Peptides such as VIP and PACAP (53) would play a role in the relaxation of some areas, including the gastric fundus and colon (54,55). Also gases such as CO (56,57) or H 2 S (58,59) are potential inhibitory neurotransmitters or neuromodulators.…”