scholarly journals Opiate Modulation of Gastrointestinal Motility and the Actions of Trimebutine

1991 ◽  
Vol 5 (5) ◽  
pp. 185-193 ◽  
Author(s):  
Stephen M Collins ◽  
Edwin E Daniel
Keyword(s):  
Postoperative Ileus ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Receptor Subtypes ◽  
Control Mechanisms ◽  
Therapeutic Approaches ◽  
Esophageal Sphincter ◽  
Irritable Bowel ◽  
Κ Receptor ◽  
Inhibitory Control Mechanisms

Trimebutine is an opiate ligand that interacts with the μ, σ and κ receptor subclasses with approximately equal affinity. Since opiate receptors are widely distributed in the gut, and because opiate receptor subtypes may be involved in excitatory or inhibitory control mechanisms, trimebutine has an unusual profile of action that cannot be predicted on the basis of experience with other synthetic opiates such as codeine, morphine or loperamide. Trimebutine influences motility throughout the gastrointestinal tract. The effect of trimcbutine on the lower esophageal sphincter raises the possibility of a beneficial role in the treatment of gastroesophageal reflex disease. The ability of trimebutine to promote propulsive activity in the fasting and postprandial small intestine offers novel therapeutic approaches to the treatment of motility disorders, including postoperative ileus and pseudo-obstruction. Finally, the effect of the drug on the colon supports the use of trimcbutine in irritable bowel syndrome patients who have constipation due to colonic inertia.

scholarly journals Comparison of [11C]Diprenorphine and [11C]Carfentanil Binding to Opiate Receptors in Humans by Positron Emission Tomography

1990 ◽  
Vol 10 (4) ◽  
pp. 484-492 ◽  
Author(s):  
J. James Frost ◽  
Helen S. Mayberg ◽  
Bernard Sadzot ◽  
Robert F. Dannals ◽  
John R. Lever ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Specific Binding ◽  
Regional Distribution ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Total Radioactivity ◽  
Emission Tomography ◽  
Receptor Subtypes ◽  
Positron Emission ◽  
Kinetics Of

The kinetics and regional distribution of [11C]carfentanil, a μ-selective opiate receptor agonist, and [11C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [11C]diprenorphine than [11C]carfentanil in all regions. [11C]Carfentanil binding (expressed as the total/nonspecific ratio) reached near equilibrium at ∼40 min, whereas [11C]diprenorphine showed a linear increase until ∼60 min. Kinetics of specific binding demonstrated significant dissociation of [11C]carfentanil from opiate receptors, whereas little dissociation of [11C]diprenorphine was observed during the 90-min scan session. Regional distributions of [11C]carfentanil and [11C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of μ-receptors), [11C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [11C]carfentanil, consistent with labeling of additional, non-μ sites by [11C]diprenorphine. We conclude from these studies that [11C]diprenorphine labels other opiate receptor subtypes in addition to the μ sites selectively labeled by [11C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor subtypes in various diseases. Development of selective tracers for the δ- and κ-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace μ, δ, and κ subtypes, will help offset these limitations.

Responses of ferret lower esophageal sphincter to 5-hydroxytryptamine: pathways and receptor subtypes

1995 ◽  
Vol 268 (6) ◽  
pp. G1004-G1011 ◽  
Author(s):  
L. A. Blackshaw ◽  
V. Nisyrios ◽  
J. Dent
Keyword(s):  
Lower Esophageal Sphincter ◽  
Splanchnic Nerve ◽  
Lower Esophageal Sphincter Pressure ◽  
Receptor Subtypes ◽  
Sphincter Pressure ◽  
In Series ◽  
Bilateral Vagotomy ◽  
Excitatory Component ◽  
Esophageal Sphincter ◽  
Greater Splanchnic Nerve

In urethananesthetized ferrets, basal lower esophageal sphincter pressure (LESP) was unaffected by the 5-hydroxytryptamine3 (5-HT3) receptor antagonist granisetron (0.5 mg/kg) or by greater splanchnic nerve section (GSX), but increased after bilateral vagotomy. Peripheral vagal nerve stimulation caused LES relaxation, often followed by a brief contraction and a prolonged inhibition of LESP. Close intra-arterial injection of 5-HT (5-100 micrograms) had a biphasic effect on LESP, with a brief drop followed by a prolonged increase. Granisetron (0.5 mg/kg i.v.) abolished the initial relaxation and revealed an earlier peak of excitation. This was not influenced by subsequent vagotomy and GSX. In a series of eight additional experiments (series 2), granisetron was given after vagotomy and GSX. In series 2, 5-HT-induced relaxation was unaffected by vagotomy but was significantly reduced after GSX and was further reduced after granisetron, indicating that 5-HT3 receptor mechanisms may lie on a sympathetic neural pathway. Vagotomy had no effect on the excitatory component. GSX had no effect on the amplitude of excitation, but reduced its latency. Granisetron had no further effect on excitation in series 2. In a separate series of 13 experiments (series 3), the excitatory component of the LES response to 5-HT was abolished by ketanserin (2.5 mg/kg i.v.) , after which only relaxation occurred. Both 5-HT2 and 5-HT3 antagonists in combination abolished all effects of 5-HT on LESP. Atropine (400 micrograms/kg i.v., n = 7) had no effect on 5-HT-induced LES responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Unraveling action selection and inhibitory control mechanisms in a striatal microcircuit model

2016 ◽  
Vol 108 ◽  
pp. 18
Author(s):  
Salva Ardid ◽  
Jason Sherfey ◽  
Michelle M. McCarthy ◽  
Joachim Hass ◽  
Nancy Kopell
Keyword(s):  
Inhibitory Control ◽  
Action Selection ◽  
Control Mechanisms ◽  
Inhibitory Control Mechanisms

Adrenocorticotropin- and opiate-like hormones from pituitaries of the sockeye salmon Oncorhynchus nerka

1987 ◽  
Vol 65 (4) ◽  
pp. 386-391 ◽  
Author(s):  
T. B. Ng ◽  
W. K. Hon ◽  
D. R. Idler
Keyword(s):  
Rat Brain ◽  
Sockeye Salmon ◽  
Oncorhynchus Nerka ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Exchange Chromatography ◽  
Acetone Powder ◽  
Rat Brain Membranes ◽  
Acetone Water ◽  
Opiate Peptides

The pituitaries of vitellogenic sockeye salmon (Oncorhynchus nerka) were extracted with a mixture of acetone, water, and hydrochloric acid. The precipitate which formed upon the addition of a copious volume of acetone to the extract, designated acid acetone powder, was subjected to salt fractionation and desalting, followed by ion-exchange chromatography on CM-cellulose. An unadsorbed fraction (S-1) and four adsorbed fractions (S-2, S-3, S-4, and S-5) were obtained. Adrenocorticotropic activity was detected in the fractions by their ability to stimulate isolated rat adrenal decapsular cells to produce corticosterone and by their immunoreactivities in an adrenocorticotropin-specific radioimmunoassay. The steroidogenic activities of all fractions, except S-4, were blocked by corticotropin inhibiting peptide. Opiate activity was detected in the fractions by their ability to inhibit the binding of either [3H]naloxone or (D-ala2,D-leu5)-[3H]enkephalin to rat brain membranes. There was a discrepancy in the potencies of the five fractions in the two opiate radioreceptor assays, indicating the presence of opiate peptides with different affinities of binding to the μ- and δ-opiate receptors of the rat brain. There was a separation between adrenocorticotropic and opiate receptor binding activities, suggesting that the activities were due to separate molecular entities.

Centrally administered naloxone blocks reflex natriuresis after acute unilateral nephrectomy

1985 ◽  
Vol 249 (3) ◽  
pp. F390-F395 ◽  
Author(s):  
S. Y. Lin ◽  
M. H. Humphreys
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Opiate Receptors ◽  
Opiate Receptor ◽  
Unilateral Nephrectomy ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Arterial Blood ◽  
Artificial Cerebrospinal Fluid ◽  
The Central Nervous System

Acute unilateral nephrectomy (AUN) leads to a natriuresis and kaliuresis by the remaining kidney through reflex mechanisms involving opiate receptors. To determine whether the opiate receptors mediating these responses are located in the central nervous system, we carried out AUN in anesthetized rats undergoing continuous ventriculocisternal perfusion (VCP) with artificial cerebrospinal fluid (CSF). AUN caused large increases in both Na (UNaV) and K (UKV) excretion without changes in glomerular filtration rate or arterial blood pressure. When the opiate receptor antagonist naloxone was added to the perfusate to achieve a perfusion rate of 32 micrograms X kg-1 X h-1, AUN failed to increase either UNaV or UKV by the remaining kidney. This dose of naloxone, however, was without effect when infused intravenously. Addition of thyrotropin-releasing hormone (TRH) to the artificial CSF to achieve a VCP rate of 50 micrograms X kg-1 X h-1 also blocked the expected increase in UNaV and UKV by the remaining kidney after AUN. Infusion of TRH intravenously at the same rate did not interfere with the postnephrectomy natriuresis or kaliuresis. Higher intravenous infusion rates of TRH (1 and 2 mg X kg-1h-1) prevented the postnephrectomy natriuresis without affecting the kaliuresis. These results indicate that the effect of naloxone to block the reflex natriuresis and kaliuresis after AUN resides largely in the central nervous system. The blockade by naloxone of the postnephrectomy natriuresis is duplicated by centrally administered TRH, providing another example of the interaction of this hormone with the endogenous opioid system. Large intravenous infusions of TRH also block the postnephrectomy natriuresis but not the kaliuresis.

Sign in / Sign up

Export Citation Format

Share Document