Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using intravital microscopy, we studied the in vivo effects of regulatory peptides on choledochoduodenal junction motility in guinea pigs. During basal and hormone-stimulated periods, intravital microscopy documented rhythmic, asymmetrical, "milking" contractions of the sphincter ductus choledochi (SDC) which occurred independent of sphincter ampullae (SA) contractions or were followed by SA contractions. Cholecystokinin octapeptide (CCK-8) (greater than or equal to 0.01 micrograms/kg) increased the frequency of SDC contractions and at higher doses (greater than or equal to 0.1 microgram/kg) increased the frequency of SA contractions. Pentagastrin (greater than or equal to 1.0 microgram/kg) and secretin (10 micrograms/kg) decreased the contraction frequencies of both sphincters. Biliary manometry demonstrated similar effects of these peptides on the frequency of the SDC and SA contractions, but also showed that CCK-8 (0.1 microgram/kg) increased the amplitude of SDC and SA contractions while pentagastrin (1 microgram/kg) decreased the amplitude of only SDC contractions. Tetrodotoxin and atropine did not affect hormone-induced changes in frequency, but tetrodotoxin reduced the increase in amplitude of contraction caused by CCK-8. We concluded that intravital microscopy provides a sensitive, in vivo technique to visualize and quantify the complex motility of a small structure like the choledochoduodenal junction.
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PMID:Intravital microscopy: a new in vivo technique for visualizing and quantifying effects of regulatory peptides on choledochoduodenal junction motility. 274 May 28

1. The results of previous studies have been in conflict with respect to the involvement of specific cholecystokinin (CCKA) and CCKB/gastrin receptors in guinea-pig gastric muscle. Here, in an in vitro, guinea-pig gastric muscle assay, pentagastrin (PG) and tetragastrin (TG) behaved as high potency agonists and produced symmetrical concentration-effect curves. In contrast, cholecystokinin-octapeptide (CCK-8), while also behaving as a high potency agonist, produced flat asymmetrical curves. Unlike recent data reported using this tissue (Boyle et al., 1993), the CCKA receptor-selective antagonist, devazepide (3, 10, 30 nM) produced a rightward shift of the upper region of the CCK-8 curve rendering it biphasic. The lower phase was abolished by the CCKB/gastrin receptor-selective antagonist, L-365260 (300 nM) indicating that the contractile effects of CCK-8 in this tissue are mediated by both receptor types. 2. L-365260 produced a concentration-dependent, parallel rightward displacement of PG concentration-effect curves. However, a flat Schild plot slope parameter (0.77 +/- 0.06) was obtained. Therefore, an empirical pA2 value of 8.64 +/- 0.21 was estimated from the smallest dose ratio. This value is consistent with published values characteristic of an interaction at CCKB/gastrin receptors. 3. TG (1 microM) was used to densensitize selectively the CCKB/gastrin receptors in the gastric muscle assay and thereby expose a population of receptors capable of responding to subsequent stimulation by CCK-8 but not by PG. The selectivity of TG for CCKB/gastrin- over CCKA receptors was demonstrated by its low efficacy compared to CCK-8 in the guinea-pig gallbladder assay, a tissue shown previously to contain a homogeneous population of CCKA receptors. In TG-desensitized gastric muscle, CCK-8 concentration-effect curves were symmetrical and could be displaced in a simple parallel fashion by devazepide at nanomolar concentrations consistent with an interaction at CCKA receptors (pKB approximately 10). 4. These results indicate that the guinea-pig gastric muscle contains both CCKA- and CCKB/gastrin receptors and the effects of CCK-8 are mediated via both of these receptors. Notwithstanding the complexity of the behaviour of L-365260, it was possible to obtain a reasonable description of the system using a simple 2-receptor model in which the effects of individual receptor activation were assumed to be additive. The absence of a simple competitive interaction of PG with L-365260 may indicate, for example, non-homogeneity of CCKB/gastrin receptors or lack of concentration equilibrium between the bath and the receptor biophase.
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PMID:The use of receptor desensitization to analyse CCKA and CCKB/gastrin receptors coupled to contraction in guinea-pig stomach muscle. 788 33

Cholecystokinin-like immunoreactive (CCK-LI) neurons are observed in the pericentral nucleus, the external nucleus and the dorsomedial part of the central nucleus of the cat's inferior colliculus. The largest number of CCK-LI cell bodies is observed in the caudal part of the pericentral nucleus. Using the electronmicroscopical examination we distinguish two different types of CCK-LI neurons. The first type CCK-LI neurons is characterized by a relatively large nucleus, surrounded by a dark rim of cytoplasm containing single cisterns of granular endoplasmic reticulum, few mitochondria and lysosomes. The second type CCK-LI neurons are smaller than the neurons of the first type. The nucleus is relatively larger while the cytoplasmic rim is quite thin. The CCK-LI immunoreactivity is also found in the large, medium-sized and small dendrites as well as in the dendritic spines. The CCK-LI axon terminals contain small round or pleomorphic vesicles. Sometimes they show a mixed population of clear and dense core vesicles. The immunoreactive terminal boutons establish typical asymmetrical synaptic contacts with dendritic spines, small or medium-sized dendrites. More rarely, the immunoreactive axon terminals perform symmetrical or intermediate synaptic contacts with proximal dendritic trunks or perikarya.
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PMID:Cholecystokinin-like immunoreactivity in cat inferior colliculus. Light and ultrastructural study. 898 8

The development of cholecystokinin-immunoreactive (CCK-IR) interneurons in the rat hippocampus was studied using immunocytochemical methods at the light and electron microscopic levels from early (P0-P8) to later postnatal (P12-P20) periods. The laminar distribution of CCK-IR cell bodies changed considerably during the studied period, which is suggested to be due to migration. CCK-IR cells appear to move from the molecular layer of the dentate gyrus to their final destination at the stratum granulosum/hilus border, and tend to concentrate in the distal third of stratum radiatum in CA1-3. The density of CCK-IR cells is rapidly decreasing during the first 4 postnatal days without any apparent reduction in their total number, therefore it is due to the pronounced growth of hippocampal volume in this period. Axons of CCK-IR interneurons formed symmetrical synapses already at P0, and by far the predominant targets were dendrites of presumed principal cells in all subfields of the hippocampus. These axon arbors began to concentrate around pyramidal cell bodies only at P8, at earlier ages CCK-IR axons crossed stratum pyramidale at right angles, and gave rise to varicose collaterals only outside this layer. The dendrites and somata of CCK-IR cells received synapses already at P0, but those were mostly symmetrical, apart from a few immature asymmetrical synapses. At P4, mature asymmetrical synapses with considerable amounts of synaptic vesicles were already commonly encountered. Thus, the innervation of CCK-IR interneurons apparently develops later than their output synapses, suggesting that they may be able to release transmitter before receiving any considerable excitatory drive. We conclude that CCK-IR cells represent one, if not the major, interneuron type that assists in the maturation of glutamatergic synapses (activation of N-methyl-D-aspartate receptors) via GABAergic depolarization of principal cell dendrites, and may contribute to the generation of giant depolarizing potentials. CCK-IR cells will change their function to perisomatic hyperpolarizing inhibition, as glutamatergic transmission in the network becomes operational.
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PMID:Postnatal development and migration of cholecystokinin-immunoreactive interneurons in rat hippocampus. 1292 99

Because obesity is a risk factor for many serious illnesses such as diabetes, better understandings of obesity and eating disorders have been attracting attention in neurobiology, psychiatry, and neuroeconomics. This paper presents future study directions by unifying (i) economic theory of addiction and obesity [4-6], and (ii) recent empirical findings in neuroeconomics and neurobiology of obesity and addiction. It is suggested that neurobiological substrates such as adiponectin, dopamine (D2 receptors), endocannabinoids, ghrelin, leptin, nesfatin-1, norepinephrine, orexin, oxytocin, serotonin, vasopressin, CCK, GLP-1, MCH, PYY, and stress hormones (e.g., CRF) in the brain (e.g., OFC, VTA, NAcc, and the hypothalamus) may determine parameters in the economic theory of obesity. Also, the importance of introducing time-inconsistent and gain/loss-asymmetrical temporal discounting (intertemporal choice) models based on Tsallis' statistics and incorporating time-perception parameters into the neuroeconomic theory is emphasized. Future directions in the application of the theory to studies in neuroeconomics and neuropsychiatry of obesity at the molecular level, which may help medical/psychopharmacological treatments of obesity (e.g., with sibutramine), are discussed.
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PMID:Toward molecular neuroeconomics of obesity. 2046 3