PACAP-(1-38) as neurotransmitter in pig pancreas: receptor activation revealed by the antagonist PACAP-(6-38)

1997 ◽  
Vol 273 (2) ◽  
pp. G436-G446 ◽  
Author(s):  
K. Tornoe ◽  
J. Hannibal ◽  
J. Fahrenkrug ◽  
J. J. Holst

The pituitary adenylyl cyclase-activating polypeptide PACAP-(1-38) has potent pancreatic secretory effects. We studied its immunohistochemical localization, release, and contribution to secretion induced by electrical vagus stimulation using isolated perfused porcine pancreas and the PACAP receptor antagonist PACAP-(6-38) (10(-7) M). PACAP was found in nerve fibers throughout the pancreas but, in particular, encircling ganglionic vasoactive intestinal polypeptide (VIP)-positive nerve cell bodies and, mostly, colocalized with VIP. Vagus stimulation caused its release. PACAP-(1-38)(4 x 10(-9) M) stimulated exocrine and endocrine secretion and released VIP. PACAP-(6-38) decreased PACAP-induced flow of juice to 59 +/- 7.8% and insulin secretion and VIP release to 12 +/- 6.8 and 57 +/- 13%, respectively. Glucagon secretion was unaffected. PACAP-(6-38) reduced vagus-stimulated flow rate to 63 +/- 7.6%, insulin and glucagon responses to 31.8 +/- 13 and 6 +/- 4%, respectively, and VIP release to 23 +/- 8.4% and reduced VIP-induced (2 x 10(-9) M) juice and insulin (but not glucagon) outputs to 8.3 +/- 4.2 and 67 +/- 14%, respectively. In conclusion, 1) pancreatic PACAP fibers seem to activate intrapancreatic VIPergic neurons, 2) PACAP-(6-38) antagonism documents the role of VIP/PACAP for neural regulation but cannot distinguish their relative importance, and 3) a PACAP receptor with low affinity for PACAP-(6-38), associated with glucagon cells, may exist.

1987 ◽  
Vol 253 (6) ◽  
pp. G767-G774 ◽  
Author(s):  
J. J. Holst ◽  
S. Knuhtsen ◽  
C. Orskov ◽  
T. Skak-Nielsen ◽  
S. S. Poulsen ◽  
...  

By immunohistochemistry, nerve fibers containing gastrin-releasing polypeptide (GRP)-like immunoreactivity were identified close to the somatostatin (SS)-producing cells of the gastric antral mucosa. We, therefore, studied the possible role of GRP in the control of antral SS secretion by use of isolated perfused pig antrum with intact vagus nerve supply. Electrical stimulation of the vagus nerves at 4 Hz increased the antral release of GRP up to 10-fold and increased SS output 2- to 3-fold. Atropine at 10(-6) M had no effect on these responses. Intra-arterial GRP increased SS secretion significantly at 10(-10) M and eightfold at 10(-8) M, whereas gastrin secretion was stimulated significantly at 10(-11) M and maximally at 10(-10) M and inhibited at 10(-8) M. Preperfusion with a GRP antagonist ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P) or Fab fragments of antibodies against GRP abolished the effects of vagus stimulation on gastrin and somatostatin output. Gastrin in concentrations up to 10(-7) M was without effect on SS secretion. We conclude that electrical stimulation of the vagus nerves increases antral SS gastrin secretion and that GRP is a likely transmitter.


1980 ◽  
Vol 238 (2) ◽  
pp. E186-E192 ◽  
Author(s):  
S. L. Jensen ◽  
J. F. Rehfeld ◽  
J. J. Holst ◽  
J. Fahrenkrug ◽  
O. V. Nielsen ◽  
...  

The effects of the four main forms of gastrin (component I, gastrin-34, gastrin-17, and gastrin-14) on insulin, glucagon, and exocrine secretion were measured on the isolated perfused porcine pancreas. All gastrins were studied in concentrations ranging from 10(-11) to 10(-8) M. Depending on the glucose concentration in the perfusate, all four gastrins increased insulin or glucagon secretion in a dose-dependent manner in concentrations above 10(-10) M. These concentrations are slightly above the arterial concentrations in normal pig and man, but they correspond to gastrin concentrations measured in patients with achlorhydria and gastrinomas. The exocrine secretion was stimulated by all gastrins in a dose-dependent manner. The lowest concentrations that stimulated flow rate significantly were within the physiologic range, 10(-11) and 10(-10) M. All gastrins induced maximal flow rate at a concentration of 10(-9) M. The sulfated form of gastrin-17 had the greatest efficacy. The results indicate that all gastrins may influence the exocrine secretion under normal conditions and the endocrine secretion in diseases with endogenous hypergastrinemia.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 355-OR ◽  
Author(s):  
YANQING ZHANG ◽  
KESHAB R. PARAJULI ◽  
GENEVIEVE E. SMITH ◽  
RAJESH GUPTA ◽  
WEIWEI XU ◽  
...  
Keyword(s):  

1961 ◽  
Vol 1 (3) ◽  
pp. 89-98
Author(s):  
Karol J. Krotki

Discussions about the role of small enterprise in economic development tend to remain inconclusive partly because of the difficulty of assessing the relative importance of economic and non-economic objectives and partly because of the dearth of factual information on which to base an economic calculus. It is probably true, moreover, that, because of a lack of general agreement as to the economic case for or against small enterprise, non-economic considerations, including some merely romantic attitudes toward smallness and bigness, tend to exert an undue influence on public policies. There may, of course, be no clear-cut economic case. And noneconomic considerations should and will inevitably weigh significantly in policy decisions. If, however, some of the economic questions could be settled by more and better knowledge, these decisions could more accurately reflect the opportunity costs of pursuing non-economic objectives.


2013 ◽  
Vol 26 (8) ◽  
pp. 1691-1699 ◽  
Author(s):  
R. A. Hufbauer ◽  
A. Rutschmann ◽  
B. Serrate ◽  
H. Vermeil de Conchard ◽  
B. Facon

2021 ◽  
pp. 186810262110186
Author(s):  
Patrik Andersson

Research confirms that China is becoming more engaged in the Arctic. However, international relations scholarship often extrapolates from relatively few instances of activity to wide-ranging claims about Chinese priorities. Fortunately, Chinese political discourse is organised by labels that allow us to study how the Arctic is classified and ranked along China’s other foreign policy priorities. This article analyses two such classifications – “important maritime interest” and “strategic new frontier,” exploring how they have come about, what they mean, and how they add political priority to the Arctic. It argues that hierarchies are constructed in two ways: by adding gradients and by including/excluding categories of priority. It views categories as performative: they not only convey information about character and relative importance of interests but are also used for achieving different objectives. By focusing on foreign policy classifications, the article contributes to a more nuanced and precise understanding of China’s Arctic interests.


Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1843-1850 ◽  
Author(s):  
E Arnaud ◽  
M Lafay ◽  
P Gaussem ◽  
V Picard ◽  
M Jandrot-Perrus ◽  
...  

Abstract An autoantibody, developed by a patient with severe and recurrent arterial thrombosis, was characterized to be directed against the anion- binding exosite of thrombin, and inhibited all thrombin interactions requiring this secondary binding site without interfering with the catalytic site. The effect of the antibody was studied on thrombin interactions with platelets and endothelial cells from human umbilical veins (HUVEC). The autoantibody specifically and concentration- dependently inhibited alpha-thrombin-induced platelet activation and prostacyclin (PGI2) synthesis from HUVEC. It had no effect when gamma- thrombin or the thrombin receptor activation peptide SFLLR were the inducers. The effect of the antibody on protein C activation has been studied. The antibody blocked the thrombin-thrombomodulin activation of protein C. The inhibition of the activation was maximal with a low concentration of thrombomodulin. The fact that the autoantibody inhibited concentration-dependent alpha-thrombin-induced platelet and endothelial cell functions emphasizes the crucial role of the anion- binding exosite of thrombin to activate its receptor. In regard to the pathology, the antibody inhibited two vascular processes implicated in thrombin-antithrombotic functions, PGI2 secretion, and protein C activation, which could be implicated in this arterial thrombotic disease.


2003 ◽  
Vol 51 (1) ◽  
pp. 45-52 ◽  
Author(s):  
László Szeredi ◽  
M. Tenk ◽  
I. Schiller ◽  

In six healthy mares and 24 mares showing reproductive disorders swab samples were taken from the fossa clitoridis to isolate Taylorella equigenitalis, and from the uterus to isolate mycoplasmas, ureaplasmas and other aerobic bacteria. Swab samples were also taken from the uterus for Chlamydiaantigen ELISA and ChlamydiaPCR studies. The uterus of 27 mares was examined cytologically, and biopsy samples were taken from the endometrium for histological examinations and for immunohistochemical examinations aimed at the detection of chlamydiae. T. equigenitalis, mycoplasmas, ureaplasmas and chlamydiae could not be detected from any of the mares examined. Aerobic facultative pathogenic bacteria were isolated from mares with endometritis in four cases. In 18 out of 22 mares with endometritis (82%) no infective agents could be demonstrated. Further studies are needed to elucidate the relative importance of non-infectious causes of endometritis and of anaerobic bacteria often detectable in the uterus in the aetiology of the reproductive disorders observed.


2017 ◽  
Vol 31 (3) ◽  
pp. 138-153 ◽  
Author(s):  
Sebastian Gurtner ◽  
Nadine Hietschold ◽  
María Vaquero Martín

Innovations in health care are costly and risky, but they also provide the opportunity for hospitals to increase quality of care, to distinguish themselves from competitors and to attract patients. While numerous hospitals strive to increase their innovativeness by adopting a costly innovation leader strategy, the question of whether this actually influences the patient’s choice remains unanswered. To understand the role of innovativeness from the patient perspective, this study conceptualizes the construct of innovativeness reputation of hospitals and determines its relevance in patients’ hospital choice decisions. In the pretest, we identified six dimensions of innovativeness reputation such as progressive work procedures and value added services. We then used three different quantitative multi-criteria decision-making methods to evaluate the relative importance of innovativeness reputation in patient choice. We collected data from 355 former German patients who had undergone elective non-emergency surgery. Overall, innovativeness reputation accounts for 11.6%–16.8% of the patient decision. Innovativeness reputation has a moderate influence on hospital choice and should be taken into account by managers. Since technical innovations are costly, hospitals should use other means to enhance their innovative image. Strategies such as emphasizing value added services can enable hospitals to increase their innovativeness reputation efficiently.


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