Differential neural regulation of circulating somatostatin-14 and somatostatin-28 in conscious dogs

1993 ◽  
Vol 264 (5) ◽  
pp. G902-G909 ◽  
Author(s):  
G. R. Greenberg

Somatostatin-like immunoreactivity (SLI) released into the circulation after nutrients or secretagogues is heterogeneous. To determine whether similar neural pathways regulate secretion of SLI molecular forms, circulating somatostatin-28 (S-28) and somatostatin-14 (S-14) responses to ingestion of a solid meal, intraduodenal perfusion of a liquid defined formula meal, and intravenous infusion of cholecystokinin octapeptide (CCK-OP, 250 pmol.kg-1.h-1) were measured in four conscious dogs with and without cryogenic blockade of the cervical vagus nerves. SLI was separated by gel-filtration chromatography of extracted, acidified plasma and quantified by radioimmunoassay. Basal plasma concentrations of S-28 were 4.1 +/- 0.6 fmol/ml and of S-14 were 3.8 +/- 0.4 fmol/ml. Ingestion of the solid meal increased plasma SLI threefold, and elevations of S-28 and S-14 were equivalent. After the intraduodenal liquid meal or infusion of CCK-OP, plasma SLI rose twofold, but increments of S-28 exceeded S-14, comprising approximately 70% of SLI released. Vagal blockade by cooling reversibly inhibited both the S-28 and S-14 responses to the solid meal, intraduodenal liquid meal, and CCK-OP. In contrast, atropine (50 micrograms/kg iv), given after solid food, intraduodenal nutrients, and CCK-OP, suppressed S-28 but further increased S-14 responses. Atropine did not, however, alter the suppression of S-14 and S-28 by vagal cooling.(ABSTRACT TRUNCATED AT 250 WORDS)

1987 ◽  
Vol 114 (1) ◽  
pp. 81-87 ◽  
Author(s):  
S. Medbak ◽  
D. F. J. Mason ◽  
L. H. Rees

ABSTRACT The involvement of endogenous opioid peptides in the stress response was investigated by measuring plasma concentrations of Met-enkephalin-like immunoreactivity (MLI), adrenaline and noradrenaline during insulin-induced hypoglycaemia in conscious greyhounds. Moreover, the molecular forms of circulating MLI were characterized using gel filtration chromatography. In the first group of animals, i.v. administration of insulin (0·3 units/kg) provoked marked hypoglycaemia (blood glucose concentrations fell from 4·4 ± 0·1 to 1·5 ±0·2 mmol/l; mean ± s.e.m.) which was associated with significant (P< 0·001) rises in plasma MLI concentrations from a basal concentration of 45 ± 8 to a peak of 189 ±39 ng/l. A within-subject study comparing five different insulin doses ranging from 0·004 to 0·3 units/kg showed dose-related effects on blood glucose with nadir concentrations of 4·1 ± 0·6 mmol/l (after the smallest dose of insulin) and 0·8 ± 0·1 mmol/l (after the largest dose of insulin). This was associated with dose-related rises in plasma MLI with peak concentrations of 56±17 and 558 ± 35 ng/l, plasma adrenaline with peak concentrations of 0·45± 0·06 and 15·76±1·33 nmol/l and plasma noradrenaline with peak concentrations of 0·49 ± 0·07 and 2·27 ± 0·45 nmol/l following the smallest and largest doses of insulin respectively. These results are the first demonstration of raised plasma MLI concentrations following hypoglycaemia. Moreover, they show that the hormonal responses vary with the degree of hypoglycaemia achieved. Together with reports by other investigators these findings might suggest opioid modulation of the responses of the sympathoadrenal system to hypoglycaemia. These responses were, however, not modified by the opioid antagonist naloxone. Gel filtration chromatography of neat (unextracted) plasma revealed the predominance of large molecular weight enkephalin-containing peptides, with approximate molecular weights of 18 000 and 8000, both basally and following stimulation by hypoglycaemia. J. Endocr. (1987) 114,81–87


1989 ◽  
Vol 257 (2) ◽  
pp. H483-H487
Author(s):  
J. W. Wiley ◽  
L. Uccioli ◽  
C. Owyang ◽  
T. Yamada

Previous reports of somatostatin's atropine-sensitive negative inotropic effect on cardiac function prompted the present studies to characterize the molecular forms and actions of somatostatin in the canine heart. Radioimmunoassay of cardiac extracts revealed concentrations of somatostatin-like immunoreactivity ranging from 0.50 +/- 0.13 pmol/g tissue (means +/- SE, n = 6) in the pulmonary artery to 0.78 +/- 0.23 pmol/g tissue in the right ventricle. On gel filtration of the extracts, two major molecular forms of somatostatin-like immunoreactivity were elicited, the predominant one coeluting with somatostatin-14 and a minor peak corresponding to somatostatin-28. Experiments performed with slices of atrial septum indicated that somatostatin-14 (10(-10) to 10(-7) M) stimulated the release of acetylcholine in a dose-dependent manner. This action of somatostatin-14 was additive with K+-evoked acetylcholine release, unaffected by hexamethonium, and blocked by tetrodotoxin, suggesting mediation via a nonnicotinic postganglionic neural pathway. Our studies lead us to conclude that somatostatin may function as a neurotransmitter in the heart, which exerts its negative inotropic action by promoting the release of acetylcholine.


1987 ◽  
Vol 113 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Ch. Foltzer ◽  
S. Harvey ◽  
P. Mialhe

ABSTRACT Variations in the concentrations of plasma and pituitary GH were determined in ducks for 66 and 87 days after hatch, and compared with somatostatin-like immunoreactivity (SLI) in the plasma, hypothalamus and neural lobe. Plasma GH levels gradually decreased during growth, while pituitary GH content increased. The concentration of pituitary GH increased during the first 3 weeks of age and remained relatively constant thereafter. The decline in plasma GH concentration was paralleled by a similar fall in the level of plasma SLI. While the content of hypothalamic SLI increased during development, the SLI concentration was maximal at 14 days of age and lowest in adults. The content and concentration of SLI in the neural lobe, in contrast, increased progressively during development. Gel filtration of hypothalamic and neural lobe extracts demonstrated that both young and older birds had two main peaks of SLI, corresponding to somatostatin-14 and somatostatin-28, and a third, larger form. The elution pattern of plasma SLI was similar in young and older birds and was principally composed of a large molecular species ('big' somatostatin), although an additional small peak eluting between somatostatin-28 and somatostatin-14 was eluted from a large pool of plasma from 90-day-old ducks. These results suggest that increased plasma GH levels in young birds do not result from a hypothalamic somatostatin deficiency nor from variations in molecular forms of SLI, and that the age-related decline in plasma GH concentration is not due to a deficiency in pituitary GH content. The decline in the circulating GH level during growth is probably due to an increase in hypothalamic somatostatin release. J. Endocr. (1987) 113, 57–63


2005 ◽  
Vol 288 (3) ◽  
pp. G487-G495 ◽  
Author(s):  
Tomio Ueno ◽  
Kenichiro Uemura ◽  
Mary B. Harris ◽  
Theodore N. Pappas ◽  
Toku Takahashi

It is generally believed that gastric emptying of solids is regulated by a coordinated motor pattern between the antrum and pylorus. We studied the role of the vagus nerve in mediating postprandial coordination between the antrum and pylorus. Force transducers were implanted on the serosal surface of the body, antrum, pylorus, and duodenum in seven dogs. Dogs were given either a solid or a liquid meal, and gastroduodenal motility was recorded over 10 h. Gastric emptying was evaluated with radiopaque markers mixed with a solid meal. Dogs were treated with hexamethonium, NG-nitro-l-arginine methyl ester (l-NAME), or transient vagal nerve blockade by cooling. A postprandial motility pattern showed three distinct phases: early, intermediate, and late. In the late phase, profound pyloric relaxations predominantly synchronized with giant antral contractions that were defined as postprandial antropyloric coordination. A gastric emptying study revealed that the time at which gastric contents entered into the duodenum occurred concomitantly with antropyloric coordination. Treatment by vagal blockade or hexamethonium significantly reduced postprandial antral contractions and pyloric relaxations of the late phase. l-NAME changed pyloric motor patterns from relaxation dominant to contraction dominant. Solid gastric emptying was significantly attenuated by treatment with hexamethonium, l-NAME, and vagal blockade. Postprandial antropyloric coordination was not seen after feeding a liquid meal. It is concluded that postprandial antropyloric coordination plays an important role to regulate gastric emptying of a solid food. Postprandial antropyloric coordination is regulated by the vagus nerve and nitrergic neurons in conscious dogs.


1996 ◽  
Vol 148 (1) ◽  
pp. 51-57 ◽  
Author(s):  
C Azizi ◽  
G Maistre ◽  
H Kalotka ◽  
R Isnard ◽  
C Barthélemy ◽  
...  

Abstract A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1–30). Plasma concentrations of proANP(1–30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1–30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1–30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1–30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity. These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1–30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP. Journal of Endocrinology (1996) 148, 51–57


1987 ◽  
Vol 113 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Ch. Foltzer ◽  
S. Harvey ◽  
P. Mialhe

ABSTRACT Pancreatic somatostatin-like immunoreactivity (SLI), immunoreactive insulin (IRI) and glucagon-like immunoreactivity (GLI) were measured during growth in ducks. The content of each hormone increased progressively but at different rates in the dorsal, ventral and splenic lobes of the pancreas. In the almost fully grown duck, the splenic lobe contained 80 and 63% of the total content of GLI and SLI respectively but low levels of IRI (23%), which were highest in the dorsal lobe (53%). In contrast to the hormonal content, only total GLI concentrations increased during development, the SLI concentrations remaining stable and IRI concentrations declining during growth. Gel filtration of pancreatic extracts indicated that most of the SLI in the pancreas of young and adult birds was somatostatin-14, although somatostatin-28 was present in the ventral lobe of young birds and larger molecular forms were present in the ventral and dorsal lobes. These changes in pancreatic hormonal content and concentration are dissimilar to age-related changes in SLI, GLI and IRI previously observed in the plasma of ducks. Plasma levels of pancreatic hormones may thus be controlled by hormonal and/or neural factors during post-hatch growth. J. Endocr. (1987) 113, 65–70


1971 ◽  
Vol 68 (3) ◽  
pp. 576-584 ◽  
Author(s):  
K. O. Nilsson ◽  
B. Hökfelt

ABSTRACT Metyrapone was administered either orally, 750 mg every four h, in a total of six doses, or intravenously 30 mg per kg body weight as a four h infusion. In three males with normal endocrine functions, metyrapone given orally or intravenously induced a fall in plasma testosterone and an elevation of androstenedione within 2–8 h. When metyrapone was administered to a patient given dexamethasone to suppress endogenous ACTH production, the androstenedione levels did not alter whereas the testosterone levels showed a slight, transient decrease. In two normal females metyrapone administration was followed by a marked increase in plasma androstenedione whereas testosterone showed only a minor, gradual increase. In one male patient with Addison's disease the basal plasma testosterone was normal whereas the level of androstenedione was low. Following metyrapone intravenously, there was a slight suppression of plasma testosterone but no change in the androstenedione concentration. In one patient with primary hypogonadism, two with secondary hypogonadism and two with Klinefelter's syndrome the plasma testosterone was low under basal conditions and did not change following metyrapone. Basal plasma androstenedione was within the range for normal males and increased markedly following metyrapone in all the cases.


1992 ◽  
Vol 262 (1) ◽  
pp. G35-G43 ◽  
Author(s):  
G. Sun ◽  
T. M. Chang ◽  
W. J. Xue ◽  
J. F. Wey ◽  
K. Y. Lee ◽  
...  

The release of cholecystokinin (CCK) and secretin into both circulation and duodenal lumen, after intraduodenal perfusion with sodium oleate or oral ingestion of fat, was studied in anesthetized and conscious dogs, respectively. Intraduodenal infusion with sodium oleate (4 mmol.kg.-1.h-1, pH 9.5) in anesthetized dogs with diversion of bile and pancreatic juice stimulated the release of both CCK and secretin not only into the circulation but also into the duodenal lumen. The concentration of CCK and secretin in the luminal perfusate increased from 0.2 +/- 0.1 to 2.1 +/- 0.4 nM and 0.34 +/- 0.16 to 2.59 +/- 0.63 nM, respectively. Intraduodenal infusion of NaHCO3 solution at pH 9.5 did not result in release of either hormone. Luminal release of both hormones was also observed by intraduodenal infusion of sodium oleate in the dogs without diversion of bile and pancreatic juice, albeit at lower concentrations than those released in the dogs with diversion. Analysis of the molecular form of luminal secretin by gel filtration, ion-exchange chromatography, and high-performance liquid chromatography showed only a single form of secretin with molecular size, hydrophobicity, and charge similar to those of natural porcine secretin. In contrast, multiple forms of CCK were released into both circulation and duodenal lumen with CCK-58 as the predominant form. In conscious dogs, CCK-58 was also found to be the predominant form of CCK released into the circulation after oral ingestion of fat.(ABSTRACT TRUNCATED AT 250 WORDS)


1979 ◽  
Author(s):  
M.J. Gallimore ◽  
E. Amundsen ◽  
M. Larsbraaten ◽  
K. Lyngaas ◽  
E. Fareid

Plasma inhibitors of plasma kallikrein(KK) were studied using chromogenic peptide substrate assays. Both “immediate” and “time-dependent” inhibition was detected. Sephadex G-150 gel filtration revealed that fractions containing α2-macroglobulin (α2 M), C1 - esterase inhibitor (CIINH) and a low molecular weight component(KKI3) gave “immediate” inhibition. When fractions were tested for “total” inhibition (incubation of enzyme plus fraction for 300 seconds at 37°C) CIINH was found to be the major inhibitor. Both the α2M and KKI3-containing fractions exhibited more inhibition than in the “immediate” inhibition assay. Studies with purified preparations of CIINH and α2 M indicated that these are the two most important plasma inhibitors of KK. Preparations of α1-antitrypsin (α1AT), antithrombin III (ATIII) and α2-antiplasmin (α2AP) produced insignificant inhibition. When “total” KK inhibition in plasma samples from 20 healthy subjects was compared with plasma concentrations of CIINH, α2M and α1AT (immunochemical assays) a very good correlation (r=0.81) was found between percentage inhibition and CIINH concentration. Correlation values for the other antiproteases were α2M r=0.36 and α1AT r=0.19.


2012 ◽  
Vol 303 (8) ◽  
pp. R850-R860 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Gordon Ohning ◽  
Yvette Taché ◽  
...  

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.


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