Localization of bovine pancreatic polypeptide (BPP)-like immunoreactivity in rat pancreatic monolayer culture

Summary Antiserum to bovine pancreatic polypeptide (BPP) has been used for immunofluorescent staining in the light microscope. With this technique it is possible to detect the presence of specific cells in monolayer culture from neonatal rat pancreas which contain BPP or a closely related peptide.This work was supported by a grant (No. 3.553.75) from the Fonds National Suisse de la Recherche Scientifique. We are very grateful to Dr.R. E. Chance, Eli Lilly, for his generous gift of BPP and anti-BPP serum. We are also very obliged to Dr.R. H. Unger for providing glucagon, to Dr.J. Rivier and Dr.R. Guillemin for somatostatin, to Dr.N. Yanaihara for secretin, to Dr.W. Gepts for gastrin and to Dr.A. J. Moody for GLI.     

Co-localization of glucagon and pancreatic polypeptide in testudine pancreas

Summary Immunocytochemistry was carried out on sections of pancreas from the gopher tortoise,Gopherus polyphemus. Combined immunofluorescent and peroxidase-anti-peroxidase techniques showed unequivocally that some of the cells were immunoreactive for both glucagon and pancreatic polypeptide (PP). Antibodies directed against avian PP, bovine PP, and human PP all have a positive reaction. Co-localization of glucagon and PP in the pancreas of the gopher tortoise indicates that the occurrence of these hormones in the same cells is widespread in higher vertebrates.Acknowledgments. This work was supported in part by grants from the University of Cape Town, the M. Crossley bequest, the N. Atkinson bequest, and Herman and Caporn bequests. The generous gifts of antisera by Dr Chance and the late Dr Kimmel, and the gift of hormones by the Lilly Research Laboratories are gratefully acknowledged. The excellent technical assistance of J. Thompson and J. B. De Haan is also gratefully acknowledged. Please send all correspondence to the USA address.     

Inhibition of neural tube closure by ionophore A23187 in chick embryos

Summary Ionophore A23187 inhibited closure of the chick neural tube through its effects on cytoskeletal components.This study was supported in part by grants from the Research Council and the Charles and Johanna Busch Memorial Fund of Rutgers University. Ionophore A23187 was provided through the courtesy of Dr R.L. Hamill, Lilly Research Laboratories, Indianapolis, Indiana, USA.     

Regional distribution of pancreatic polypeptide cells in the 21-day fetal rat pancreas

Summary 21-day fetal rat pancreata were stained with the unlabeled antibody peroxidase-antiperoxidase technique using bovine pancreatic polypeptide as the primary antibody. Total counts of pancreatic polypeptide cells were made over the entire pancreas. It was found that the head region contained the greatest number of pancreatic polypeptide cells with the body next and the tail having the smallest number. The pancreatic polypeptide cells of the body were concentrated in the portion closest to the distal duodenum. This distribution pattern seems to support the suggested role of pancreatic polypeptide on the physiological function of the digestive tract.The authors wish to express their appreciation to Dr R. McEvoy, T. Whittlsey, G. Wassilchenko and D. Wilson for their assistance in this study. To whom reprint requests should be addressed.     

Pancreatic polypeptide: A possible role in the regulation of food intake in the mouse. Hypothesis

Summary Pancreatic polypeptide (PP) is a recently identified hormone produced by pancreatic endocrine cells. The islets of genetically obese mice (ob/ob, C57 BL/6J), which are suspected to lack a circulating satiety factor, contain relatively few of the PP-producing cells. Administration of bovine pancreatic polypeptide (bPP) reduces food intake and suppresses body weight gain in the hyperphagic obese mice. It is postulated that PP participates in the regulation of food intake in a manner as yet undefined.This work was supported by grant No. 3.553.75 from Swiss National Science Foundation. We thank Mrs M. Eissler and Mr R. Cuche for their valuable help.     

The glucose dependence of pancreatic endocrine responses to 2-deoxyglucose in the calf

Summary The initial plasma glucose concentration of unanesthetized calves with cut splanchnic nerves, given 2-deoxyglucose (1.2 mmoles/kg, i.v.), was either lowered by prior starvation, or raised by a continuous infusion of exogenous glucose. Raising the initial plasma glucose concentration completely suppressed the release of pancreatic glucagon and pancreatic polypeptide but substantially enhanced the release of insulin in response to 2-deoxyglucose.This work has been supported by the Medical Research Council and the Leverhulme Trust. We are also indebted to Mr P.M.M. Bircham and Mr G.P. Macgregor for their skilled technical assistance.     

Release of gastrointestinal hormones following an oral water load

Summary The ingestion of 2 different water loads (7.5 and 15 ml/kg) by healthy subjects stimulated the release of plasma motilin, gastrin, pancreatic polypeptide and VIP. Atropine was found to block the release of PP but not the other hormones.This work was made possible by generous grants by the Wellcome Trust and Medical Research Council.     

Profound hypothermia in golden hamsters (Mesocricetus auratus) induced by serotonergic potentiating and noradrenergic inhibiting drugs

Summary Profound hypothermia (6°C) was induced in cold exposed golden hamsters (Mesocricetus auratus) by a combination of drugs that potentiate brain serotonergic activity (fluoxetine and pargyline) and inhibit noradrenergic activity (alpha-methyl-p-tyrosine). Individual drugs and combinations of 2 were ineffective.Acknowledgements. We acknowledge the support of a research grant PCM74-05158 A01 to A.H.M. from the National Science Foundation (USA) and thank Lilly Research Laboratories, Indianapolis, Indiana, for the gift of fluoxetine (Lilly 110140).     

Immunohistochemical localization of pancreatic polypeptide (PP) in the brain of the larval instar of the hoverfly,Eristalis aenus (Diptera)

Summary 2 pancreatic polypeptide (PP) immunoreactive cells were observed in each half of the protocerebrum of the last (5th), larval instar of the hoverfly,Eristalis aenus. No PP immunoreactive nerve fibers could be detected in the brain.Support by a grant from the Swedish Medical Research Council (project No. 12X-102) and by a Swedish Institute scholarship.     

Glucagon and pancreatic polypeptide immunoreactivities co-exist in a population of rat islet cells

In mammalian pancreas, glucagon and pancreatic polypeptide have been shown to be present in distinct cell types. The present communication reports that, in rat pancreas, in addition to glucagon and pancreatic polypeptide cell populations, there is a small population of cells which contain both glucagon and pancreatic polypeptide immunoreactivities.     

Glucagon and pancreatic polypeptide immunoreactivities co-exist in a population of rat islet cells

Summary In mammalian pancreas, glucagon and pancreatic polypeptide have been shown to be present in distinct cell types. The present communication reports that, in rat pancreas, in addition to glucagon and pancreatic polypeptide cell populations, there is a small population of cells which contain both glucagon and pancreatic polypeptide immunoreactivities.     

Effect of long acting somatostatin-analogue, SMS 201 995, on gut hormone secretion in normal subjects

SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s.c. injection of 50 micrograms it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.     

Effect of long acting somatostatin-analogue,SMS 201995, on gut hormone secretion in normal subjects

Summary SMS 201 995 is a new long acting analogue of somatostatin. We have investigated its effect on basal and meal stimulated secretion of gut hormones and have shown that after a single s. c. injection of 50 g it lowers significantly the basal plasma levels of pancreatic polypeptide, secretin, motilin, pancreatic glucagon and insulin, it also effectively suppresses the postprandial release of pancreatic polypeptide, gastrin, secretin, gastric inhibitory peptide, pancreatic glucagon and insulin. Except for the usual brief discomfort of an injection, no symptoms or untoward effects were observed.     

Presence of "pancreatic polypeptide" cells, and gastrin immunoreactivity in immuno-induced exocrine pancreas carcinoma]

1) In electively immuno-induced carcinomas of the exocrine pancrease in Mice, where A (glucagon) and B (insulin) endocrine cells persist, cells with a pancreatic polypeptide immunoreactivity are also detected, even in late evolution stages. These cells, like D cells, containing somatostatin, are localized only in the pancreatic remains surrounding the anaplasic carcinomatous tissue: islets, adenomatous parenchyma, and ductular epithelium. Ultrastructure of these cells shows their active elaboration of numerous chracteristic secretion granules. (2) Immunocytoenzymatic detection of gastrin is negative in the exocrine and endocrine pancreatic tissues. However one of the anti-gastrin sera used gives a positive reaction, in some carinomatous cells only. Does this immunoreactivity characterize a polypeptide specific to the pancreatic carcinomatous cell?     

The effect of Apamin® on nonadrenergic,noncholinergic nervous vasodilatations in the cat small intestine

Summary The intestinal vasodilation evoked by mechanical mucosal stimulation or by transmural electrical field stimulation was abolished by close i.a. injection of Apamin, a polypeptide originally isolated from bee venom. Apamin also blocked the vasodilatation induced by close i.a. infusion of vasoactive intestinal polypeptide (VIP). It is suggested that Apamin is a VIP receptor antagonist.This research was sponsored by grants from the Swedish Medical Research Council (14X-2855), from the Swedish Society for Medical Sciences, from Magnus Bergvalls Stiftelse and from the Medical Faculty, University of Göteborg.     

Localization of bovine pancreatic polypeptide (BPP)-like immunoreactivity in rat pancreatic monolayer culture.

Antiserum to bovine pancreatic polypeptide (BPP) has been used for immunofluorescent staining in the light microscope. With this technique it is possible to detect the presence of specific cells in monolayer culture from neonatal rat pancreas which contain BPP or a closely related peptide.     

Effect of pancreatic duct ligation on exocrine pancreatic function and structure in the rabbit

Summary 4 weeks after pancreatic duct ligation in the rabbit, fecal and luminal chymotrypsin were detected in concentrations similar to the control group. Pancreatic changes in the ligated group were marked dilatation of the main pancreatic duct, proliferation and distention of ductules and fibrosis. Despite pancreatic duct ligation and fibrosis, proteolytic enzymes continued to secrete into the duodenal lumen. These results suggest that pancreatic duct ligation in the rabbit is not associated with total pancreatic insufficiency.This study was supported by the Kansas University Endowment Association (Grant No. 73-2550), General Research Support (Grant No. 2553 and 1522-14) and a grant from Kaw Valley Heart Association.     

Interaction between 6-hydroxydopamine and rhodopsin in vivo in the rat retina

Résumé Nous avons observé que l'injection de la 6-hydroxydopamine dans l'humeur vitrée des rats adaptés à la lumière bloquait le rétablissement de la sensibilité rétinale pendant l'adaptation à l'obscurité subséquente au traitement. Il est possible que cette observation soit une conséquence de la réaction du produit de l'oxydation de la 6-hydroxydopamine avec les groupes nucléophiliques de la rhodopsine.

---

---

This study was partially supported by Postdoctoral Training Grant No. MH 10965 to S.F.P. and by Eli Lilly Co., Research to Prevent Blindness, Inc., and NSF No. GB-39853 to L.T.G. Samples of 6-aminodopamine were kindly supplied by Drs.R. N. Adams (University of Kansas, Lawrence, Kansas) andE. L. Engelhardt (Merck Sharp and Dohme Res. Labs. West Point, Pa.) andp-quinone by Dr.P. A. Wehrli (Hoffmann-La Roche, Nutley, New Jersey). The authors thank Mr.L. Tomey for excellent technical assistance.     

Endocrine cells producing regulatory peptides

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Preliminary observations on the co-existence of regulatory peptides in cells of the baboon endocrine pancreas

Summary Immunocytochemical procedures at ultrastructural and light microscopy level revealed, in the Chacma baboon endocrine pancreas, cells which were immunoreactive for glucagon and pancreatic polypeptide (PP). Some D cells were observed to contain secretory granules with both the appearance and immunoreactivity of A cell secretory granules.