Acid inhibition by intestinal nutrients mediated by CCK-A receptors but not plasma CCK

Lloyd, Kevin C K; Wang, Jiafang; Solomon, Travis E.

doi:10.1152/ajpgi.2001.281.4.g924

Cited by 6 publications

(3 citation statements)

References 33 publications

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“…Others reported peak levels after SBTI (28,30) or SO (19) to be Ͻ11 pM compared with 20 pM observed in our laboratory. However, basal levels reported in other studies were lower than those observed in the present study (Ͻ1 pM compared with our 8 pM) as were the increases after secretagogue infusion (up to 16-fold compared with our 2.5-fold).…”

Section: Discussioncontrasting

confidence: 57%

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

Sartor¹,

Shulkes²,

Verberne³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Sartor, Daniela M., Arthur Shulkes, and Anthony J. M. Verberne. An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats. Am J Physiol Regul Integr Comp Physiol 290: R625-R633, 2006. First published October 20, 2005 doi:10.1152/ajpregu.00639.2005.-Ingestion of a meal results in gastrointestinal (GI) hyperemia and is associated with systemic and paracrine release of a number of peptide hormones, including cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT). Systemic administration of CCK octapeptide inhibits a subset of presympathetic neurons of the rostroventrolateral medulla (RVLM) that may be responsible for driving the sympathetic vasomotor tone to the GI viscera. The aim of this study was to determine whether endogenous release of CCK and/or 5-HT also inhibits CCK-sensitive RVLM neurons. The effects of intraduodenal administration of the secretagogues sodium oleate (SO) and soybean trypsin inhibitor (SBTI) on circulating levels of CCK and 5-HT were examined. In separate experiments, the discharge rates of barosensitive, medullospinal, CCK-sensitive RVLM presympathetic vasomotor neurons were recorded after rapid intraduodenal infusion of SO-SBTI or water. Alternatively, animals were pretreated with the CCK 1 receptor antagonists devazepide and lorglumide or the 5-HT 3 antagonist MDL-72222 before SO-SBTI administration. Secretagogue infusion significantly increased the level of circulating CCK, but not 5-HT. SO-SBTI significantly decreased (58%) the neuronal firing rate of CCKsensitive RVLM neurons compared with water (5%). CCK 1 receptor antagonists did not reverse SO-SBTI-induced neuronal inhibition (58%), whereas the 5-HT 3 antagonist significantly attenuated the effect (22%). This study demonstrates a functional relation between a subset of RVLM presympathetic vasomotor neurons and meal-related signals arising from the GI tract. It is likely that endogenously released 5-HT acts in a paracrine fashion on GI 5-HT 3 receptors to initiate reflex inhibition of these neurons, resulting in GI vasodilatation by withdrawal of sympathetic tone. rostroventrolateral medulla; cholecystokinin; devazepide; MDL-72222; 5-hydroxytryptamine GASTROINTESTINAL HYPEREMIA is a physiological consequence of food consumption. Gastrointestinal hormones such as cholecystokinin (CCK) have been implicated in gastrointestinal vasodilatation associated with postprandial increase in splanchnic blood flow. The involvement of the sympathetic vasomotor system in this response is poorly understood. We recently suggested that food-related signals may produce gastrointestinal vasodilatation via a reflex withdrawal of sympathetic vasomotor outflow (39,45). In healthy individuals, the sympathetic nervous system compensates for postprandial splanchnic blood pooling by activating sympathetic vasoconstrictor drive to skeletal muscle resistance vessels in response to baroreceptor unloading. In patients with cardiovascular disease associated with diabetic neuropathy or autonomic dysfunction, poor baroreflex comp...

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Section: Discussioncontrasting

confidence: 57%

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

Sartor¹,

Shulkes²,

Verberne³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In the oxyntic mucosa, CCK was shown to control histamine release (Chen et al 2004). This mechanism was also demonstrated in the rat (Woltman & Reidelberger, 1999;Lloyd et al 1992Lloyd et al , 2001, in sheep (Zavros & Shulkes, 1997) and in man (Schmidt et al 1994) via occupation of the CCK 2 receptors present on the ECL cells (Modlin & Tang, 1996).…”

Section: Global Effects Of Gastrin and Cholecystokinin In The Gutmentioning

confidence: 83%

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

et al. 2006

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The aim of the present review is to synthesise and summarise our recent knowledge on the involvement of cholecystokinin (CCK) and gastrin peptides and their receptors in the control of digestive functions and more generally their role in the field of nutrition in mammals. First, we examined the release of these peptides from the gut, focusing on their molecular forms, the factors regulating their release and the signalling pathways mediating their effects. Second, general physiological effects of CCK and gastrin peptides are described with regard to their specific receptors and the role of CCK on vagal mucosal afferent nerve activities. Local effects of CCK and gastrin in the gut are also reported, including gut development, gastrointestinal motility and control of pancreatic functions through vagal afferent pathways, including NO. Third, some examples of the intervention of the CCK and gastrin peptides are exposed in diseases, taking into account intervention of the classical receptor subtypes (CCK 1 and CCK 2 receptors) and their heterodimerisation as well as CCK-C receptor subtype. Finally, applications and future challenges are suggested in the nutritional field (performances) and in therapy with regards to the molecular forms or in relation with the type of receptor as well as new techniques to be utilised in detection or in therapy of disease. In conclusion, the present review underlines recent developments in this field: CCK and gastrin peptides and their receptors are the key factor of nutritional aspects; a better understanding of the mechanisms involved may increase the efficiency of the nutritional functions and the treatment of abnormalities under pathological conditions.

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“…GRP mediates its effects by gastrin release and it may also be an important neurotransmitter in the vagal–cholinergic pathway, as demonstrated by the GRP antagonist BIM26226, which blocks vagally mediated acid secretion in humans in similar ways to atropine [37]. CCK may also function as a physiologic inhibitor induced by the presence of nutrients in the intestine [38,39]. Other inhibitors of acid secretion that stimulate somatostatin release include glucagon-like peptide, CCK, VIP, leptin, amylin and EGF.…”

Section: Physiology Of Acid Secretionmentioning

confidence: 99%

Acid peptic diseases: pharmacological approach to treatment

Mejia

Kraft

2009

Expert Review of Clinical Pharmacology

102

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Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases.

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Acid inhibition by intestinal nutrients mediated by CCK-A receptors but not plasma CCK

Cited by 6 publications

References 33 publications

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

Acid peptic diseases: pharmacological approach to treatment

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