The effect of dimethyl PGE2 on canine pancreatic autograft exocrine secretion

Garvin, Paul J.; Niehoff, Michael L.; Burton, Frank R.

doi:10.1016/0022-4804(89)90168-6

Cited by 2 publications

(1 citation statement)

References 14 publications

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“…Previous work on pancreatitis, an inflammatory disorder that is associated with high serum amylase content, found that PGE 2 treatment blocks amylase secretion from pancreatic acini ( Mössner et al, 1991 ). Furthermore, canines with allograft pancreatic transplants that were treated with dimethyl-PGE 2 had reduced amylase levels in urine compared to untreated controls, indicative of improved pancreatic function with PGE 2 ( Garvin et al, 1989 ). Indomethacin treatment has been shown to increase isoproterenol (ISO)-induced amylase secretion from rat parotid gland tissue, where enhanced amylase secretion observed following ISO (0.1 μM) stimulation was abrogated by co-treatment with PGE 2 ( Hata et al, 1990 ).…”

Section: Discussionmentioning

confidence: 99%

Indomethacin Treatment Post-irradiation Improves Mouse Parotid Salivary Gland Function via Modulation of Prostaglandin E2 Signaling

Gilman

Camden

Woods

et al. 2021

Front. Bioeng. Biotechnol.

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Annually, >600,000 new cases of head and neck cancer (HNC) are diagnosed worldwide with primary treatment being surgery and radiotherapy. During ionizing radiation (IR) treatment of HNC, healthy salivary glands are collaterally damaged, leading to loss of function that severely diminishes the quality of life for patients due to increased health complications, including oral infections and sores, cavities, and malnutrition, among others. Therapies for salivary hypofunction are ineffective and largely palliative, indicating a need for further research to uncover effective approaches to prevent or restore loss of salivary gland function following radiotherapy. Previous work in our lab implicated prostaglandin E2 (PGE2) as an inflammatory mediator whose release from radiation-exposed cells promotes salivary gland damage and loss of function. Deletion of the P2X7 purinergic receptor for extracellular ATP reduces PGE2 secretion in irradiated primary parotid gland cells, and salivary gland function is enhanced in irradiated P2X7R–/– mice compared to wild-type mice. However, the role of PGE2 signaling in irradiated salivary glands is unclear and understanding the mechanism of PGE2 action is a goal of this study. Results show that treatment of irradiated mice with the non-steroidal anti-inflammatory drug (NSAID) indomethacin, which reduces PGE2 production via inhibition of cyclooxygenase-1 (COX-1), improves salivary gland function compared to irradiated vehicle-treated mice. To define the signaling pathway whereby PGE2 induces salivary gland dysfunction, primary parotid gland cells treated with PGE2 have increased c-Jun N-terminal Kinase (JNK) activation and cell proliferation and reduced amylase levels and store-operated calcium entry (SOCE). The in vivo effects of blocking PGE2 production were also examined and irradiated mice receiving indomethacin injections have reduced JNK activity at 8 days post-irradiation and reduced proliferation and increased amylase levels at day 30, as compared to irradiated mice without indomethacin. Combined, these data suggest a mechanism whereby irradiation-induced PGE2 signaling to JNK blocks critical steps in saliva secretion manifested by a decrease in the quality (diminished amylase) and quantity (loss of calcium channel activity) of saliva, that can be restored with indomethacin. These findings encourage further attempts evaluating indomethacin as a viable therapeutic option to prevent damage to salivary glands caused by irradiation of HNC in humans.

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Section: Discussionmentioning

confidence: 99%

Indomethacin Treatment Post-irradiation Improves Mouse Parotid Salivary Gland Function via Modulation of Prostaglandin E2 Signaling

Gilman

Camden

Woods

et al. 2021

Front. Bioeng. Biotechnol.

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Factors affecting measurement of urinary amylase after bladder‐drained pancreas transplantation

Nankivell,

Allen,

Bell

et al. 1991

Clinical Transplantation

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Abstract:Urinary amylase activity (UA) was evaluated in 14 diabetic patients receiving bladder‐drained whole pancreas transplants. Amylase was dependent upon pH with optimal activity at pH 7. Increasing acidity led to a substantial loss of measured UA (45% remaining at pH 4, 73% at pH 5, 86% at pH 6, p < 0.001); however, UA was stable at room temperature if the pH was kept constant. On the day after transplantation, a transient peak in UA was followed by a trough lasting a median of 3 days. Thereafter the UA rose steadily, with the rate of rise being faster if the pancreas donor was less than 30 years of age (p < 0.05). Maximal UA values were observed between 3‐6 months after transplantation. High protein and fat liquid test meals, designed to stimulate exocrine secretion, produced an 83% rise in UA (p = 0.02), which was not observed when water was given (n = 8, p = 0.007, differences at 1 hour). Fasting for 17.6 ± 2.1 h (mean ± SEM) produced a 29 ± 6% fall in 24‐h UA, without any measurable change in other parameters of renal or pancreatic function. A fall of 50% in 24‐h UA over 7 d was compared with pancreas biopsy (n = 40) for predicting rejection, and showed a sensitivity of 60% and a specificity of 93%. In 3 patients a false‐negative result occurred in the first few days after transplantation at a time when the UA failed to rise as normally expected. Understanding and eliminating some of the factors which cause variability in UA may improve the interpretation of 24‐h UA measurements in bladder‐drained pancreas allografts.

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The effect of dimethyl PGE2 on canine pancreatic autograft exocrine secretion

Cited by 2 publications

References 14 publications

Indomethacin Treatment Post-irradiation Improves Mouse Parotid Salivary Gland Function via Modulation of Prostaglandin E2 Signaling

Indomethacin Treatment Post-irradiation Improves Mouse Parotid Salivary Gland Function via Modulation of Prostaglandin E2 Signaling

Factors affecting measurement of urinary amylase after bladder‐drained pancreas transplantation

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