Both
galanin and
substance P have been separately implicated in the pathogenesis of
acute pancreatitis. We compared the efficacy of the combination of the
galanin antagonist
galantide and the
neurokinin-1 receptor antagonist L703,606 with that of either alone in the treatment of
acute pancreatitis.
Acute pancreatitis was induced in mice with 7-hourly
caerulein injections.
Galantide was co-administered with each
caerulein injection commencing with the first injection (prophylactic) or 2h after the first injection (therapeutic). L703,606 was administered either 30 min before (prophylactic), or 2h after the first
caerulein injection (therapeutic). Combination of the two agents was also administered. Control groups received
galantide, L703,606, or saline, without
caerulein. Pancreata were harvested for histological examination and estimation of
myeloperoxidase activity. Plasma
amylase activity was measured. Prophylactic and therapeutic administration of
galantide reduced the
hyperamylasemia by 37% and 30% respectively whereas only prophylactic L703,606 reduced
hyperamylasemia (by 34%). Prophylactic administration of the combined antagonists reduced the
hyperamylasemia by 44%. In contrast, therapeutic administration of the combination significantly increased plasma
amylase levels by 27%. The plasma
amylase activity in the control groups was similar to basal levels. Prophylactic and therapeutic administration of either antagonist or the combination significantly reduced
myeloperoxidase activity.
Galantide and L703,606 individually, and in combination, significantly reduced the
acute pancreatitis-induced
necrosis score. The administration of the combined antagonists does not offer any further benefit as compared to
galantide alone. An interaction between neurokinin-1 and
galanin receptors may occur to modulate
amylase secretion.