The regulation of basal pancreatic polypeptide levels in dogs

George A. Werther, Mark A. Sperling, Stephen Joffe, Richard F. Murphy

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

In response to to various stimuli, pancreatic polypeptide (PP) release is predominantly mediated by cholinergic mechanisms, and may be modulated by sympathetic and opiate (inhibitory) effects. However, the mechanisms regulating basal PP levels remain unclear. We examined the possible role of the sympathetic nervous system and endogenous opiates in the regulation of basal levels of pancreatic polypeptide in trained conscious dogs. During prolonged (150 min) α- or β-adrenergic blockade with phentolamine and propranolol, separately or in combination, there was no change in the basal PP levels of 154 ± 20 pg/ml. Effective adrenergic modulation of pancreatic hormones was evident since α blockade led to a rise in insulin and glucagon, β blockade led to a fall in insulin and glucagon, while combined α- and β-adrenergic blockade did not affect insulin or glucagon. Opiate blockade with naloxone (1.25 mg followed by 1 μg/kg/min) led to a delayed fall in PP from 153 ± 22 to 89 ± 15 pg/ml at 90 min (no change by 30 min), without a change of insulin or glucagon. Infusion of a potent morphine analogue d-Met2-Pro5-enkephalinamide (0.5 μg/kg/min) led to a sustained fall in PP to 91 ± 8 pg/ml by 30 min without a change in insulin or glucagon. Somatostatin infusion (0.2 μg/kg/min) with insulin and glucagon replacement, led to a similar sustained fall in PP. It is concluded that in dogs: (1) in contrast to insulin and glucagon, at basal conditions the plasma level of PP is not modulated by endogenous α- or β-adrenergic influences; (2) opiate tone does not appear to be involved in the maintenance of basal PP levels; the delayed suppression by high-dose naloxone most likely represents a naloxone agonist effect; (3) the mechanism of the opiate (and high dose naloxone) inhibitory effect is probably not mediated by somatostatin, since insulin and glucagon were unaffected.

Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalRegulatory Peptides
Volume17
Issue number4
DOIs
StatePublished - Apr 1987
Externally publishedYes

Keywords

  • Autonomic regulation
  • Glucagon
  • Opiate
  • Somatostatin

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