Vasoactive Intestinal Peptide: A Secretin-Like Partial Agonist for Pancreatic Secretion in Man

Domschke, S; Domschke, Wolfram; Rösch, Wolfgang; Konturek, Stanisław J.; Sprügel, W.; Mitznegg, P; Wünsch, Erich; Demling, L

doi:10.1016/s0016-5085(19)32126-2

Cited by 45 publications

(9 citation statements)

References 17 publications

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“…VIP was first isolated from hog duodenum by Said & Mutt (1972) and has been shown to share nine amino acid residues with porcine secretin when the two peptides are aligned from the NH2-terminus (Table 1) (Mutt & Said, 1974). In rat, 0022 9 o~o°o * 5 3v V ACTION OF VIP ON THE AVIAN PANCREAS dog and man the maximum rate of flow of pancreatic juice evoked by VIP is 15-20% that evoked by secretin (Dockray, 1973; Konturek, Thor, Dembinski & Krol, 1975; Domschke, Domschke, Rosch, Konturek, Sprugel, Mitznegg, Wunsch & Demling, 1977). In the cat, the maximum rates of flow of pancreatic juice stimulated by secretin and VIP are similar, but VIP is about twenty times less potent than secretin on a molar basis (Konturek, Pucher & Radecki, 1976).…”

Section: Introductionmentioning

confidence: 99%

Potent stimulation of the avian exocrine pancreas by porcine and chicken vasoactive intestinal peptide.

Dimaline¹,

Dockray²

1979

The Journal of Physiology

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SUMMARY1. The actions of chicken and porcine secreting and vasoactive intestinal peptides (VIPs) were compared on the rate of flow and rate of protein secretion from the exocrine pancreas in urethane anaesthetized turkeys and rats.2. Chicken VIP was about twice as potent as porcine VIP and 100-150 times as potent as chicken and porcine secreting in stimulating the flow of pancreatic juice in the turkey.3. Porcine secretin was a strong stimulant of the flow of pancreatic juice in the rat, but chicken secretin and the two VIPs were only active in doses 20-50 times higher than those of porcine secretin.4. Neither the two VIPs nor the two secreting significantly stimulated the rate of pancreatic protein secretion in the turkey or rat.5. In the turkey i.v. infusion of graded doses of chicken VIP produced graded increases in the flow of pancreatic juice; in the presence of an infusion of a low dose of CCK8 the flow of juice secreted in response to the highest dose of chicken VIP was significantly lower compared with the infusion of VIP alone, and responses to the other doses of VIP were lower but not significantly so. The infusion of chicken secretin reduced the flow of juice in response to infusions of chicken VIP, but the differences were not significant. There was no significant difference in either the rate of flow, or rate of protein secretion from the turkey pancreas in response to an infusion of chicken secretin and CCK8, compared with CCK8 alone.6. The results cast doubt on the importance of secretin for regulation of the avian pancreas, and suggest instead that VIP might have a physiological role in regulating the flow of pancreatic juice in birds.

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Section: Introductionmentioning

confidence: 99%

Potent stimulation of the avian exocrine pancreas by porcine and chicken vasoactive intestinal peptide.

Dimaline¹,

Dockray²

1979

The Journal of Physiology

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“…Recently some systemic effects of exogenously administered VIP were evaluated in man (Domschke et al, 1977): VIP acts as a secretin-like partial agonist of human pancreatic exocrine secretion. To 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.…”

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confidence: 99%

Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects.

Domschke¹,

Domschke²,

Bloom³

et al. 1978

Gut

123

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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.

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“…The potency of VIP as a stimulant of pancreatic secretion is low in all species (9,10,15,16); this together with the finding that VIP is released from the intestine into the circulation only by non-physiological intraluminal stimuli ( 7 ) makes it unlikely that VIP subserves an endocrine role in the control of pancreatic secretion. The physiological significance of VIP must be viewed in the context ofa local humoral (i.e.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of Synthetic and Natural Vasoactive Intestinal Peptide on Pancreatic and Biliary Secretion and on Glucose and Insulin Blood Levels in the Dog

Makhlouf

Yau

Zfass

et al. 1978

Scandinavian Journal of Gastroenterology

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The effects of synetic porcine vasoactive intestinal peptide (VIP) on pancreatic and biliary secretion and on glucose, insulin and calcium blood levels were examined in the dog and compared with the effects of natural porcine VIP. Synthetic VIP was a secretin-like partial agonist of pancreatic and biliary secretion with efficacies relative to secretin of 0.27 and 0.41, respectively. Consistent with its weak secretin-like action, synthetic VIP augmented the pancreatic response to CCK-OP and the submaximal but not the maximal response to secretin. Synthetic VIP also produced a dose-dependent increase in blood glucose levels and a synchronous and proportionate increase in blood insulin levels. A slight increase in total calcium levels was equivocal. The effects of antural VIP on pancreatic and biliary secretion and on glucose and insulin blood levels were identical to those of synthetic VIP. The identity of effects supports the validity of the postulated structure of porcine VIP. Although elicited at high doses, the effects of VIP on exocrine and endocrine secretion may be relevant physiologically in the context of a neurocrine or paracrine role for VIP.

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Vasoactive Intestinal Peptide: A Secretin-Like Partial Agonist for Pancreatic Secretion in Man

Cited by 45 publications

References 17 publications

Potent stimulation of the avian exocrine pancreas by porcine and chicken vasoactive intestinal peptide.

Potent stimulation of the avian exocrine pancreas by porcine and chicken vasoactive intestinal peptide.

Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects.

Comparative Effects of Synthetic and Natural Vasoactive Intestinal Peptide on Pancreatic and Biliary Secretion and on Glucose and Insulin Blood Levels in the Dog

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