Circulating galanin: origin, metabolism, and pharmacokinetics in anesthetized pigs

The concentration of galanin-like immunoreactivity (GAL-LI) was 12.9 +/- 0.9 pmol/l in porcine arterial plasma (n = 9) and ranged from 1 to 14 pmol/g in extracts of porcine gastrointestinal tract (n = 5), the colon being the richest gut segment. A significant (P less than 0.05) arteriovenous concentration difference of circulating endogenous GAL-LI occurred across the kidney (15.1 +/- 2.3 vs. 6.2 +/- 0.5 pmol/l) and a hind leg (15.7 +/- 2.5 vs. 10.2 +/- 1.0 pmol/l), whereas a negative gradient was observed across the intestine (12.5 +/- 2.0 vs. 17.7 +/- 3.3 pmol/l) of anesthetized pigs. Passage through the brain, liver, or lungs did not change the concentration of endogenous GAL-LI significantly. During basal circumstances, the major source of circulating GAL-LI is therefore the gut. During infusion of 20 pmol.kg-1.min-1 of synthetic porcine galanin, a significant extraction occurred across the kidney (64.8 +/- 4.3%), hind leg (20.3 +/- 3.8%), and liver (19.7 +/- 4.3%). The overall metabolic clearance rate was 37.8 +/- 3.7 ml.min-1.kg-1. The half-life of galanin in plasma was 4.6 +/- 0.3 min, and the apparent distribution space was 255.6 +/- 31.4 ml/kg. Incubation studies in vitro showed that the concentration of galanin, added to blood and plasma at 37 degrees C, was halved in 1 h, unless stabilized with EDTA and aprotinin.