Adrenergic Pathways Do Not Mediate Peptide YY-Induced Inhibition of Pancreatic Exocrine Secretion

Abstract

The influence of extrapancreatic nerves and intrapancreatic adrenergic activity on the inhibition of pancreatic exocrine secretion by peptide YY (PYY) was studied in conscious dogs. Chronic pancreatic fistulae were created in five mongrel dogs while a second group of five dogs also underwent complete pancreatic denervation. After recovery, a continuous infusion of secretin (62 ng/kg/h) and cholecystokinin (CCK; 50 ng/kg/h) was administered over 2 h. An infusion of PYY (400 pmol/kg/h) was then given randomly, during either the first or second experimental hour. The experiments were then replicated after establishing adrenergic blockade with continuous background infusions of either phentolamine (0.2 mg/kg/ h), propranolol (0.5 mg/kg bolus) or a combination of phentolamine and propranolol. The secretinicholecystokinin-induced bicarbonate and protein outputs were significantly inhibited by PYY in both the innervated and denervated animals. Adrenergic blockade failed to eliminate the inhibitory effects of PYY. We conclude that extrapancreatic neural pathways, including adrenergic mechanisms, do not mediate the inhibitory effects of PYY. The results suggest that PYY inhibits secretidcholecystokinin-induced pancreatic response by an indirect nonadrenergic mechanism.

The islet-acinar axis of the pancreas: more than just insulin

“…On the basis of further studies, peptide YY appears to act via intrapancreatic cholinergic nerves and independent of adrenergic nerves and pancreatic blood flow (22,23,32,33). The contribution of pancreatic blood flow on the observed effects of peptide YY in the pancreas cannot be ruled out since Sheikh et al (172), using a slide-mount autoradiographic technique on frozen sections of rat pancreas, were able to demonstrate autoradiographic Y1 receptor localization predominantly over vascular smooth muscle cells and not to acinar cells.…”

Overview of Exocrine Pancreatic Pathobiology

“…Peptide YY (PYY) is structurally similar to pancreatic polypeptide and significantly inhibits secretin- and CCK- stimulated pancreatic exocrine secretion (Tatemoto, 1982). PYY acts via intrapancreatic cholinergic nerves and is independent of adrenergic nerves or extrapancreatic nerves (DeMar et al ., 1991; Brodish et al ., 1993; Brodish et al ., 1995). Peptide YY acts via the Y1 receptor in rats and Y2 receptor in dogs (Grandt et al ., 1995; Teyssen et al ., 1996).…”

Slowing intestinal transit by PYY depends on serotonergic and opioid pathways

“…To test for the slowing of intestinal transit, PYY (200 pM⅐kg Ϫ1 ⅐h Ϫ1 ) (Bachem, Torrance, CA) or equivolume (0.15 M NaCl; control) was delivered intravenously for 90 min beginning at the start of intestinal perfusion. This dose of PYY was chosen because it is within the physiological range (100-400 pM⅐kg Ϫ1 ⅐h Ϫ1 ) that is effective in increasing intestinal water and electrolyte absorption (4,5,39), in delaying phase III of migrating motor complexes (52), in inhibiting gastric acid secretion (19,56), and in inhibiting pancreatic secretion in dogs (7,50).…”