Plasma concentrations of cholecystokinin octapeptide and food intake in male rats treated with cholecystokinin octapeptide

1989 ◽  
Vol 121 (1) ◽  
pp. 59-65 ◽  
Author(s):  
A. Lindén ◽  
K. Uvnäs-Moberg ◽  
G. Forsberg ◽  
I. Bednar ◽  
P. Södersten

ABSTRACT Intraperitoneal injection of 5 μg cholecystokinin octapeptide (CCK-8) into male rats deprived of food for 48 h produced a transient (less than 15 min) increase in plasma levels of CCK-8 but suppressed food intake for an extended period (45 min). Plasma concentrations of CCK-8 after i.p. injection of CCK-8 were raised to levels which were fairly comparable to those after feeding. Intracerebroventricular (i.c.v.) injection of the CCK antagonist proglumide (100 μg) reversed the effect of CCK-8 on food intake, while i.p. injection of proglumide (100 μg) did not have this effect. Feeding increased the plasma concentrations of somatostatin and gastrin but not of oxytocin, and somatostatin and oxytocin but not gastrin were released in response to i.p. injection of CCK-8. However, neither somatostatin nor oxytocin affected food intake, and their release in response to CCK-8 was unaffected by i.c.v. injection of proglumide. These results support the suggestion that CCK-8 is a physiological 'satiety' peptide, which can affect food intake in rats by mechanisms involving both peripheral and central CCK receptors. Journal of Endocrinology (1989) 121, 59–65

1991 ◽  
Vol 3 (5) ◽  
pp. 491-496 ◽  
Author(s):  
I. Bednar ◽  
G. Forsberg ◽  
A. Lindén ◽  
G. A. Qureshi ◽  
P. Södersten

1975 ◽  
Vol 66 (2) ◽  
pp. 183-193 ◽  
Author(s):  
D. GUPTA ◽  
K. RAGER ◽  
J. ZARZYCKI ◽  
M. EICHNER

SUMMARY Plasma concentrations of LH, FSH, testosterone and dihydrotestosterone (DHT) have been measured in normal sexually maturing male rats from the age of 16–90 days. Between 16 and 25 days plasma testosterone levels were low, but rose suddenly on day 26. A similar increment occurred at the same time in plasma DHT levels, but this steroid reached its peak concentration later than testosterone. Plasma LH levels rose steadily from day 25 onwards, reaching their highest values on day 30. A marked increase in FSH levels was found on day 16, and a peak was reached on day 33 followed by a decline to a level characteristic of the adult. In addition, plasma levels of all these hormones were estimated in the male animals at various stages of development after orchidectomy and cryptorchidism. Four days after operation, the plasma levels of LH and FSH in the orchidectomized animals reached higher levels than those found in the intact animals, indicating the existence of a dynamic feedback relationship before puberty between gonadal steroids and pituitary gonadotrophic secretion. However, results from the experimental bilaterally cryptorchid animals, suggested that the gonadal steroid–gonadotrophic feedback relationship could not be the only factor initiating puberty.


1991 ◽  
Vol 261 (3) ◽  
pp. R614-R618 ◽  
Author(s):  
T. C. Kirkham ◽  
J. Gibbs ◽  
G. P. Smith

The abdominal site or sites for the satiety action of exogenous, peripherally administered bombesin (BN) were investigated. By use of a chronic arterial catheterization technique, the effects of 1, 2, and 4 micrograms/kg BN on liquid food intake of nondeprived male rats were assessed. Comparisons were made between the effects of these doses infused into the celiac or superior mesenteric arteries or injected intraperitoneally. The satiating potency of exogenous BN was significantly enhanced by direct administration into the celiac artery, which directly perfuses the stomach, pancreas, liver, spleen, and proximal duodenum. By this route, 4 micrograms/kg BN produced greater than 60% suppression of 15-min food intake. By contrast, BN infused into the superior mesenteric artery was no more effective than intraperitoneal injection. Celiac infusion of 1 micrograms/kg BN produced a suppression (30%) of intake that was equivalent to, or exceeded, that obtained after intraperitoneal injection or superior mesenteric infusion of 4 micrograms/kg. These results strongly support an upper abdominal, and possibly gastric, site for the satiety action of peripherally administered BN.


1984 ◽  
Vol 246 (5) ◽  
pp. G543-G549 ◽  
Author(s):  
R. D. Reidelberger ◽  
M. O'Rourke ◽  
P. R. Durie ◽  
M. C. Geokas ◽  
C. Largman

Concentrations of plasma immunoreactive anionic and cationic trypsin(ogen) were monitored in unanesthetized dogs to investigate diurnal variation, response to food intake, and effects of cholecystokinin octapeptide (CCK-8) plus secretin administration. Identical meals were consumed at the beginning and end of a 24-h period. Plasma levels of both trypsin(ogen)s increased significantly within 30 min of feeding. Second-meal responses were much larger than those following the first meal. Plasma cationic trypsin(ogen) was also elevated during the normal feeding period when food was withheld and dogs in adjacent cages were fed. Small, irregular variations in plasma trypsin(ogen)s occurred during the interdigestive period when blood was sampled every 2 h. CCK-8 plus secretin, in doses shown previously to stimulate exocrine secretion of enzymes submaximally, increased plasma levels of both trypsin(ogen)s dose dependently. Most (greater than 80%) of the immunoreactive cationic trypsin(ogen) in plasma before and after feeding and following CCK-8 was in proenzyme form. We conclude that plasma levels of pancreatic trypsinogens are increased by food intake and low doses of CCK-8. Furthermore, cephalic mechanisms appear to play an important role in mediating the response to food intake.


1979 ◽  
Vol 91 (3) ◽  
pp. 473-483 ◽  
Author(s):  
C. van Hardeveld ◽  
M. J. Zuidwijk ◽  
A. A. H. Kassenaar

ABSTRACT Rats were exposed to cold (4°C) for 1 and 4 weeks. The T4 plasma concentrations initially declined (24.5 ± 7.7 nmol/l) after 1 week but returned to normal levels after 4 weeks (52.9 ± 14.2 nmol/l). The T3 concentrations were elevated after both 1 and 4 weeks at 4°C (1.31 ± 0.21 and 1.38 ± 0.12 nmol/l, respectively). Control values (23°C) for T4 were 42.6 ± 10.3 and for T3 1.11 ± 0.13 nmol/l. Addition of 0.015 g KI/l to the drinking water prevented the T4 decrease in plasma after 1 week of cold exposure. No effect of iodide was observed at 23°C. The suppletion of KI did not change pattern of T3 increase after cold exposure. After 4 weeks of cold exposure the T4 levels of the iodide-supplemented animals did not differ from the non-supplemented group. No evidence was found that increased food intake is a contributory factor in the development leading to increased T3 plasma levels during cold exposure.


Author(s):  
Elizabeth R Houston ◽  
Sarah M Tan ◽  
Samantha M Thomas ◽  
Ulana L Stasula ◽  
Mollie K Burton ◽  
...  

Buprenorphine (Bup) is an opioid analgesic that is commonly used in laboratory rodents to provide postoperative analgesia. However, dosing every 4 to 6 h is necessary to maintain an analgesic plasma concentration of the drug. A long lasting,highly concentrated veterinary formulation of Bup (LHC-Bup) has been used to provide prolonged analgesia in cats and nonhuman primates. In the current study, we evaluated the duration of efficacy of LHC-Bup to determine if this formulation would provide a similarly prolonged analgesia in rats. Drug concentrations were measured after subcutaneous injectionof 0.5 mg/kg LHC-Bup in both male and female rats. Plasma levels were measured at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and72 h. Male and female rats had peak plasma levels of LHC-Bup at 90 ng/and 34 ng/mL, respectively, at 15 min after administration, with a steady decrease by 24 h to 0.7 ng/mL in males and 1.3 ng/mL in females. Mechanical pain tolerance wasevaluated after LHC-Bup administration using a Randall-Selitto analgesiometer to assess paw withdrawal. Male rats had a significantly longer paw withdrawal time for up to 12 h after administration, and females had longer paw withdrawal timesfor up to 24 h. An experimental laparotomy model was then used to assess the clinical efficacy of LHC-Bup at 0.5 mg/kg. LHC-Bup treatment was associated with a greater total distance traveled, reduced time to retrieve a food treat, and reduced grooming from 3 to 12 h after surgery as compared with saline controls. Groups receiving LHC-Bup showed coprophagy whereas other rats did not. These results suggest that administering LHC-Bup at 0.5 mg/kg provides therapeutic plasma concentrations for 12 to 24 h after administration and analgesic efficacy for at least 12 h after dosing. As such, LHC-Bup is a suitable alternative to Bup-HCl.


1987 ◽  
Vol 115 (1) ◽  
pp. 91-95 ◽  
Author(s):  
A. Linden ◽  
S. Hansen ◽  
I. Bednar ◽  
G. Forsberg ◽  
P. Södersten ◽  
...  

ABSTRACT Male rats deprived of food for 48 h ignored food pellets immediately after ejaculating with a sexually receptive female rat as did males tested 5 min after i.p. injection of 5 μg cholecystokinin octapeptide (CCK-8) or males which had consumed food pellets for 1 h. The concentration of CCK-8 in plasma was increased to comparable levels (10·1±3·8 (s.e.m.); 11·3 ± 3·7 and 7·2± 0·5 pmol/l respectively, compared with 1·2 ± 0·3 pmol/l for NaCl-injected controls) under each of these conditions, whereas the concentration of gastrin increased only after food consumption (18·4 ± 3·8; 17·7 ± 5·4 and 54·3± 7·0 pmol/l respectively, compared with 21·5 ± 2·1 pmol/l for NaCl-injected controls). The effect of ejaculation on the latency to starting to eat was partially reversed by i.p. injection of 50 mg of the CCK-8 antagonist proglumide, but neither treatment with proglumide or CCK-8 nor consumption of food affected the display of sexual behaviour. The results support the suggestion that CCK-8 is a 'satiety peptide' in the rat. J. Endocr. (1987) 115, 91–95


1999 ◽  
Vol 82 (11) ◽  
pp. 1428-1432 ◽  
Author(s):  
Cheryl Scott ◽  
Francesco Salerno ◽  
Elettra Lorenzano ◽  
Werner Müller-Esterl ◽  
Angelo Agostoni ◽  
...  

SummaryLittle is known about the regulation of high-molecular-weight-kininogen (HK) and low-molecular-weight-kininogen (LK) or the relationship of each to the degree of liver function impairment in patients with cirrhosis. In this study, we evaluated HK and LK quantitatively by a recently described particle concentration fluorescence immunoassay (PCFIA) and qualitatively by SDS PAGE and immunoblotting analyses in plasma from 33 patients with cirrhosis presenting various degrees of impairment of liver function. Thirty-three healthy subjects served as normal controls. Patients with cirrhosis had significantly lower plasma levels of HK (median 49 μg/ml [range 22-99 μg/ml]) and LK (58 μg/ml [15-100 μg/ml]) than normal subjects (HK 83 μg/ml [65-115 μg/ml]; LK 80 μg/ml [45-120 μg/ml]) (p < 0.0001). The plasma concentrations of HK and LK were directly related to plasma levels of cholinesterase (P < 0.0001) and albumin (P < 0.0001 and P < 0.001) and inversely to the Child-Pugh score (P < 0.0001) and to prothrombin time ratio (P < 0.0001) (reflecting the clinical and laboratory abnormalities in liver disease). Similar to normal individuals, in patients with cirrhosis, plasma HK and LK levels paralleled one another, suggesting that a coordinate regulation of those proteins persists in liver disease. SDS PAGE and immunoblotting analyses of kininogens in cirrhotic plasma showed a pattern similar to that observed in normal controls for LK (a single band at 66 kDa) with some lower molecular weight forms noted in cirrhotic plasma. A slight increase of cleavage of HK (a major band at 130 kDa and a faint but increased band at 107 kDa) was evident. The increased cleavage of HK was confirmed by the lower cleaved kininogen index (CKI), as compared to normal controls. These data suggest a defect in hepatic synthesis as well as increased destructive cleavage of both kininogens in plasma from patients with cirrhosis. The decrease of important regulatory proteins like kininogens may contribute to the imbalance in coagulation and fibrinolytic systems, which frequently occurs in cirrhotic patients.


1987 ◽  
Vol 58 (03) ◽  
pp. 850-852 ◽  
Author(s):  
M B McCrohan ◽  
S W Huang ◽  
J W Sleasman ◽  
P A Klein ◽  
K J Kao

SummaryThe use of plasma thrombospondin (TSP) concentration was investigated as an indicator of intravascular platelet activation. Patients (n = 20) with diseases that have known vasculitis were included in the study. The range and the mean of plasma TSP concentrations of patients with vasculitis were 117 ng/ml to 6500 ng/ml and 791±1412 ng/ml (mean ± SD); the range and the mean of plasma TSP concentrations of control individuals (n = 33) were 13 ng/ml to 137 ng/ml and 59±29 ng/ml. When plasma TSP concentrations were correlated with plasma concentrations of another platelet activation marker, β-thromboglobulin (P-TG), it was found that the TSP concentration inei eased exponentially as the plasma β-TG level rose. A positive correlation between plasma levels of plasma TSP and serum fibrin degradation products was also observed. The results suggest that platelets are the primary source of plasma TSP in patients with various vasculitis and that plasma TSP can be a better indicator than β-TG to assess intravascular platelet activation due to its longer circulation half life.


1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.


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