To accommodate the intake of food or liquid, gastric reservoir functions are importantas the physiological reflex. There exist two major responses as a reservoir function of the stomach ; adaptive and receptive relaxations. Adaptive relaxation is a reflex in which the fundus of the stomach dilates in response to small increases in intragastric pressure when food enters the stomach. Receptive relaxation is a reflex in which the gastric fundus dilates when food passes down the pharynx and the esophagus. The mechanisms of these two types of functional responses are to some extent different, although a nitric oxide (NO)-dependent non-adrenergic, non-cholinergic neural pathway is involved in the both relaxation reflexes. Adaptive relaxation is an intragastric pressure-induced reflex . Stretch of the gastric wall activates the mechanoreceptors in gastric mucosa (Mu), which generate impulses carried by the capsaicin-sensitive afferent sensory neuron . The sensory neuron can synapse on the inhibitory efferent neuron directly or activate it via interneurons of the myenteric plexus. This leads to the release of NO from the nitroxergic efferent neuron, which causes relaxation of circular muscle and hence of the fundus . Alternatively, an axon reflex causes the NO release from the sensory neuron, resulting in hexamethonium-resistant gastric relaxation. Receptive relaxation is mediated by vagal motor fibers. In contrast with the pressure-induced adaptive relaxation, ganglionic nicotinic transmission is essential in the vagally-induced relaxation. VIP and CGRP are important neurotransmitters of the inhibitory sensory neuron, which, however, may not mediate both adaptive and receptive relaxations. Disorders of these reservoir functions result in symptoms of early satiety and anorexia, which are the major symptoms of patients with functional dyspepsia.

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The effects of extracellular Ca²⁺ ions on purinergic responses were examined in swine tracheal smooth muscle cells (TSMCs) in primary culture. ATP (1μM to 1mM) and α, β methylene adenosine 5'-triphosphate (α, β-Me ATP) (100μM and 1mM) concentration-dependently increased [Ca²⁺] in the presence and the absence of extracellular Ca²⁺ . Responses to ATP (10μM to 1mM) in the presence of extracellular Ca²⁺ were significantly larger than those in its absence (n=8), whereas those to α, β-Me ATP were not significantly different between the presence (n=7) and the absence (n=8) of extracellular Ca²⁺ . Responses to ATP (1mM) at extracellular Ca²⁺ concentration ([Ca²⁺] _o) of 10 and 5mM were significantly larger than that at extracellular EGTA concentration ([EGTA] _o) of 1mM (p<0.01, n=5), whereas the responses to α, β-Me ATP (1mM) at 10 and 5mM [Ca²⁺] _o were significantly smaller than that at [EGTA] _o of 1mM (p<0.05, n=5). Increasing [Ca²⁺] _o to 5mM after the application of either 1mM ATP (n=4) or 1mM α, β-Me ATP (n=4) in the absence of extracellular Ca²⁺ (1mM [EGTA] _o) further increased [Ca²⁺] _i, though the increases in [Ca²⁺] _i, by agonists in 1mM [EGTA] _o had been already maximal. Incubating cells for 300s in 5mM [Ca²⁺] _o before the application of ATP (1mM) significantly increased the response to the drug than that obtained by incubating cells for 6sec in 5mM [Ca²⁺] _o before the drug application (p<0.01, n=4). However, α, β-Me ATP (1mM) induced similar responses by incubating cells for 30 or 300s in 5mM [Ca²⁺] _o to that by incubating them for 6s. These results suggest that the effect of α, β-Me ATP in swine TSMCs in primary culture is mainly through Ca²⁺ release and that its effect on Ca²⁺ entry is smaller than other nucleotides.

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To understand the receptor subtypes responsible for β-adrenoceptor-mediated relaxation of guinea pig taenia caecum, we investigated the effects of isoprenaline and salbutamol . Isoprenaline and salbutamol caused dose-dependent relaxation of the guinea pig taenia caecum. Propranolol, bupranolol and butoxamine produced shifts of the concentration response curves for isoprenaline and salbutamol. Schild regression analyses carried out for propranolol against isoprenaline and salbutamol gave pA₂ values of 8.43 and 8.88, respectively. Schild regression analyses carried out for butoxamine against isoprenaline and salbutamol gave pA₂ values of 6.46 and 6.68, respectively. Schild regression analyses carried out for bupranolol against isoprenaline and salbutamol gave pA₂ values of 8.60 and 8.69, respectively. However, in the presence of 3 × 10^-4 M atenolol, 10^-4 M butoxamine and 10^-6 M phentolamine to block the β₁-, β₂- and α -adrenoceptor effects, respectively, Schild regression analyses carried out for bupranolol against isoprenaline and salbutamol gave pA₂ values of 5.77 and 5.97, respectively. These results suggest that the relaxant responses to isoprenaline and salbutamol in the guinea pig taenia caecum are mediated by both the β₂- and the β₃-adrenoceptors.

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We examined the characteristics of the non-adrenergic, non-cholinergic (NANC) inhibitory response of the circular muscle of the rat stomach fundus to transmural nerve stimulation or high K⁺. Treatments with isotonic high K⁺ (20mM), nitric oxide (NO) and sodium nitroprusside (SNP) all elevated cyclic GMP levels in the rat stomach fundus in the presence of atropine and guanethidine. Isotonic high K⁺-induced formation of cyclic GMP was completely inhibited by tetrodotoxin (TTX) or N^G-nitro-L-arginine (L-NNA). The K⁺ also increased cyclic AMP levels and this response was completely inhibited by TTX. Dose-dependent relaxation of the fundus in response to SNP was shifted to the right by a prior incubation with high concentration of SNP (10^-4M) for 2hrs. Incubating the fundus with SNP for 2hrs significantly inhibited NO-induced cyclic GMP formation. Relaxation responses to transmural stimulation (1Hz or 30Hz), isotonic high K⁺ and NO were significantly reduced by a prior incubation with SNP. Isotonic high K⁺ (20mM)-induced relaxation of circular muscle strips was not completely inhibited by combined treatment with 10^-5M L-NNA, 5×10^-5M oxyhemoglobin and anti-VIP (1: 200). These results suggest that NO as well as VIP is possible transmitter from NANC nerves in the circular muscle of the rat stomach fundus and there should be one or more inhibitory mediators other than VIP and NO.

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Platelet activating factor (PAF) is known to produce a wide veriety of hemodynamic effects . The present study was carried out with the aim of elucidating the mechanism of PAF action on vosoconstrictive response to noradrenaline (NA-R) in the presence of autologous platelets. NA-R was examined in isolated perfused arterial segments. PAF action through stimulation of platelets by noradrenaline (NA) was explored during infusion of platelet rich plasma (PRP) with PAF into the perfusion circuit. Consequently, it was revealed that PRP with PAF elicited an initially augmented response, followed by gradually attenuated responses under conditions of low doses of NA (in the range of 5 to 25ng). However, the augmented responses were observed consistently under a higher dose of NA (50ng). In addition, the gradually attenuated responses were reversed by adding tetrodotoxin, a Na-spike inhibitor. Thus, it is concluded that PAF action on NA-R through platelets may be related partly to neurotransmitters originating from perivascular autonomic depressant nerves stimulated by some neuroeffector agents.

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Purines of ATP, ADP, AMP and adenosine released from rat caudal artery with and without endothelium and the isolated smooth muscle and endothelial cells were examined, in order to determine the source. Treatment of intact segments of caudal arteries with noradrenaline (10μM) for 3min induced a large release of ATP, ADP, AMP and adenosine.However, if the artery segments had been denuded of their endothelial lining, noradrenaline induced only a slight release of purines. Endothelial cells in primary culture prepared from caudal arteries, when exposed to noradrenaline for 3min released large amounts of purines, whereas vascular smooth muscle cells prepared similarly and passaged endothelial cells did not release purines upon exposure to noradrenaline. These results indicate that, of smooth muscle and endothelial cells of the vascular wall, only intact endothelial cells react to α adrenoceptorstimulation by releasing adenine nucleotides and adenosine.

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