Lack of effect of the specific cholecystokinin receptor antagonist loxiglumide on cholecystokinin clearance from plasma in man.

Jebbink, M. C. W.; Jansen, J. B. M. J.; Masclee, Ad; Lamers, C. B. H. W.

doi:10.1111/j.1365-2125.1990.tb03701.x

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…We did so by the minimalist assumption that the mean rate at which EPSPs arrive is proportional to the CCK concentration in plasma, which decays exponentially to zero after bolus injection. The decay of plasma CCK estimated in the current study from the recordings of oxytocin cells (230 seconds) is close to the half-life of CCK measured in human plasma (about 4 minutes) ( 42 ).…”

Section: Discussionsupporting

confidence: 83%

A Predictive, Quantitative Model of Spiking Activity and Stimulus-Secretion Coupling in Oxytocin Neurons

2018

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Oxytocin neurons of the rat hypothalamus project to the posterior pituitary, where they secrete their products into the bloodstream. The pattern and quantity of that release depends on the afferent inputs to the neurons, on their intrinsic membrane properties, and on nonlinear interactions between spiking activity and exocytosis: A given number of spikes will trigger more secretion when they arrive close together. Here we present a quantitative computational model of oxytocin neurons that can replicate the results of a wide variety of published experiments. The spiking model mimics electrophysiological data of oxytocin cells responding to cholecystokinin (CCK), a peptide produced in the gut after food intake. The secretion model matches results from in vitro experiments on stimulus-secretion coupling in the posterior pituitary. We mimic the plasma clearance of oxytocin with a two-compartment model, replicating the dynamics observed experimentally after infusion and injection of oxytocin. Combining these models allows us to infer, from measurements of oxytocin in plasma, the spiking activity of the oxytocin neurons that produced that secretion. We have tested these inferences with experimental data on oxytocin secretion and spiking activity in response to intravenous injections of CCK. We show how intrinsic mechanisms of the oxytocin neurons determine this relationship: In particular, we show that the presence of an afterhyperpolarization (AHP) in oxytocin neurons dramatically reduces the variability of their spiking activity and even more markedly reduces the variability of oxytocin secretion. The AHP thus acts as a filter, protecting the final product of oxytocin cells from noisy fluctuations.

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Section: Discussionsupporting

confidence: 83%

A Predictive, Quantitative Model of Spiking Activity and Stimulus-Secretion Coupling in Oxytocin Neurons

2018

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“…It was also observed during infusion of the CCK analogue cerulein [22]. When CCK-8 was infused, antagonist treat ment slightly increased plasma CCK concen trations in one study [3], but had no efect in further studies [23,24].…”

Section: Discussionmentioning

confidence: 91%

CCK Receptor Antagonist Loxiglumide Alters Uptake of CCK in Perfused Liver and Pancreatic Acini of the Rat

Beckh

Göke²,

Ruff³

et al. 1991

Digestion

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The aim of the present study was to analyze the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on hepatic and pancreatic processing of CCK-8 and the CCK analogue cerulein. Rat liver perfusion was performed in a non-recirculating system. CCK concentrations were measured by radioimmunoassay in perfusates from the inflow cannula (portal vein) and the outflow cannula (hepatic vein). In rat pancreatic acini, the effect of loxiglumide on internalization and surface-binding of radiolabelled CCK-8 was determined. Cerulein (20 nM, 2 nM) was extracted in a single pass through the liver by 29.7 and 25.4%, respectively. The hepatic uptake of CCK-8 (50 pM, 2 nM) was more than 90 and 89.9%, respectively. Loxiglumide drastically inhibited hepatic extraction of both peptides and reduced internalization of ¹²⁵I-CCK-8 in pancreatic acini dose dependently by 39–93%. These results demonstrate that the potent CCK receptor antagonist loxiglumide significantly decreased CCK uptake by the liver and pancreas.

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“…In previous studies we have demonstrated that the first explanation is less likely [33]. However, specific type A CCK-receptors have been demonstrated on SST-producing cells [35], and in a recent study we have demonstrated that inhibition of SST release by CCK-receptor blockade might be the explanation for the augmented BBS-stimulated gastric acid secretion and serum gastrin release during loxiglumide infusion [36].…”

Section: Discussionmentioning

confidence: 88%

Effect of duodenal juice on bombesin‐stimulated cholecystokinin release during loxigIumide administration in man

Jebbink¹,

Jansen²,

Kleij³

et al. 1993

Eur J Clin Investigation

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Abstract. Stimulation of cholecystokinin release by bombesin is augmented by cholecystokinin receptor blockade with loxiglumide. We hypothesize that this augmented cholecystokinin release results from inhibition of the pancreatico-biliary response to bombesin during cholecystokinin receptor blockade. To test this hypothesis, we infused bombesin for 180 min in six healthy subjects Three bombesin-infusion experiments were performed in each subject in random order on different days. In two of these experiments loxiglumide was co-infused with bombesin, while in the third experiment saline was co-infused with bombesin. In one of the loxiglumide experiments, duodenal juice, collected on the previous day during infusion of cholecystokinin-GIH, was reperfused intraduodenally during the second hour of bombesin infusion.In the saline experiment, the integrated cholecystokinin response during the first hour of bombesininfusion (262 f 63 pmol 60 min-I) was significantly ( P < 0.01) higher than during the second (88 +26 pmol 60 min-') and third (87f31 pmol 60 min-l) hour of bombesin-infusion. Loxiglumide augmented bombesin-stimulated cholecystokinin secretion from 262 f 63 pmol 60 min-I to 453 63 pmol 60 min-' in the first hour of bombesin infusion (P

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Lack of effect of the specific cholecystokinin receptor antagonist loxiglumide on cholecystokinin clearance from plasma in man.

Cited by 8 publications

References 18 publications

A Predictive, Quantitative Model of Spiking Activity and Stimulus-Secretion Coupling in Oxytocin Neurons

A Predictive, Quantitative Model of Spiking Activity and Stimulus-Secretion Coupling in Oxytocin Neurons

CCK Receptor Antagonist Loxiglumide Alters Uptake of CCK in Perfused Liver and Pancreatic Acini of the Rat

Effect of duodenal juice on bombesin‐stimulated cholecystokinin release during loxigIumide administration in man

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