No abstract

SUMMARY Graded doses of 0-6, 1'3, and 3.3 pmol/kg/min of vasoactive intestinal peptide (VIP) were intravenously infused over 30 minute periods in four healthy volunteers and plasma VIP levels were measured by radioimmunoassay. Even with the smallest dose of VIP, plasma concentrations rose markedly above normal values. Infusion of higher VIP doses resulted in mean plateau levels of circulating VIP which were in the range of VIP values found in the Verner-Morrison syndrome. After cessation of the VIP infusions, plasma VIP levels fell strikingly by first order kinetics with an average disappearance half-time of one minute. The apparent metabolic clearance rate was about 9 ml/kg/min and the apparent volume of distribution for VIP was approximately 14 ml/kg. During infusion of the highest VIP dose, previously shown to induce one-fifth maximum pancreatic juice secretion, plasma concentrations of glucose, free fatty acids, and calcium were slightly but significantly raised, the pulse rate and the amplitude of blood pressure were increased, and cutaneous flushing occurred. The spectrum of effects accords well with some abnormalities seen in the Verner-Morrison syndrome. The present data, however, do not support a role for VIP as a circulating hormone, at least under physiological conditions.Vasoactive intestinal peptide (VIP) was originally isolated from hog small intestine (Said and Mutt, 1970). It has been found in high concentrations not only in the entire gastrointestinal tract Polak et al., 1974) but it has also been shown to be present in central and peripheral neurons (Bryant et al., 1976;Said and Rosenberg, 1976).It remains a matter of debate whether VIP predominantly acts as a local tissue hormone, plays its major role as a neurotransmitter substance, or acts as a circulating hormone (Bryant et al., 1976 levels of VIP had been produced by the originally administered VIP infusions, the same VIP dosage was repeated in additional volunteers and the plasma levels of VIP were measured. On the data obtained a pharmacokinetic analysis was performed. In addition, some routine laboratory parameters were assessed. MethodsFour healthy male volunteers (mean age 23 + 1 years, mean body weight 72 ± 2 kg) with no history or physical findings of gastrointestinal or renal diseases were studied. All subjects gave informed written consent. The experimental protocol had been approved by the Local Ethical Committee. On separate days, in random order, four series of tests were done on each subject. After an overnight fast, the individual study was started. Through an indwelling antecubital catheter, saline solution (0-15 M NaCI) was infused at 30 ml/h with a syringe pump (Model 71100, Braun, Melsungen, W. Germany) for a basal period of 30 minutes. Then 1049 on 13 May 2018 by guest. Protected by copyright.

In rat brain slices preincubated with various radiolabelled putative neurotransmitters, methionine-enkephalin diminished the potassium-evoked release of dopamine and acetylcholine. The effect was antagonised by naloxone. The potassium-induced effux of three other neurotransmitters, histamine, 5-hydroxy-tryptamine and gamma-aminobutyric acid, were unaffected by methionine-enkephalin. A probable physiological function for the endogenous ligands in specifically affecting the catecholaminergic and cholinergic transmission is suggested.

SUMMARY The dose response of duodenal bicarbonate production during synthetic porcine secretin infusions was studied in six healthy volunteers and related to plasma secretin immunoreactivity. Secretin was infused in each individual at four different doses from 0