The effects of VIP on intestinal motility study onex vivo perfused isolated canine jejunal loops

Abstract

The effects of VIP on intestinal motility were studied on isolated canine jejunal loops ex vivo perfused at normothermia, under pulsatile flow with heparinized, oxygenated and nonrecirculated canine whole blood, by means of an intraluminal balloon. VIP was administered intraarterially either by 1 min injections or by long-time infusions. The results showed that for arterial concentrations of the polypeptide ranging between 25 pg/ml and 300-500 pg/ml a fast but short-lasting relaxant effect was observed. For higher concentrations VIP usually produced a biphasic response: The relaxant effect is followed by an increase of the basal muscular tone often accompanied, for concentrations higher than about 25 ng/ml, by a marked and transient increase in amplitude of the intestinal rhythmic contractions. During long-time infusions a biphasic response was also observed but both effects were of short duration. A cholingeric origin of the secondary contracting phase was expected but could not be demonstrated because, at blood concentrations at which atropine affected the biphasic response, not only was the contractile effect abolished but also the initial relaxing phase. It is suggested that the secondary contraction may be a "rebound excitation" of myogenic nature or a result of noncholingeric excitatory fiber stimulations. The short-lasting relaxant effect observed under the present experimental conditions, even during long-time infusion of the polypeptide, fails to argue for an important physiological role of VIP as an hormonal inhibitor of intestinal motility. The biphasic response, however, might have a physiological significance in so far as the aboral propulsion of the intestinal content requires a muscular inhibition which rapidly changes to contraction.

Do Elevated Plasma Vasoactive Intestinal Polypeptide (VIP) Levels Cause Small Intestinal Motor Disturbances in Humans?

“…These alterations took place within about 5 min. Thereafter, motility recurred to normal patterns despite ongoing VIP infusion (23). Consequently, protracted VIP infusion over several hours might have obscured an initial inhibitory effect in our experiments and we may have missed potential effects of short-lasting VIP infusion on human small intestinal motility.…”

“…In vivo studies investigating the effect of VIP infusion on human gastrointestinal motility are lacking, so far, but there are several studies performed in rats, dogs, and pigs which have yielded conflicting results: disruption of the migrating motor complex (19,20), reduction of antral and duodenal motility (15)(16)(17)(18)22) or even induction of motor quiescence (19,20), shortening of small intestinal MMC interval (22), and retardation of small intestinal transit (21) have been observed in response to high doses of VIP. However, there are also several studies failing to show (major) effects of VIP infusion on gastrointestinal motility (4,18,22,23). Using isolated muscle preparations from various regions of the gastrointestinal tract in pigs, Mandrek and Milenov demonstrated that VIP potently inhibits tonic contractions of the duodenal circular muscle layer but has no effect on the contractility of the longitudinal muscle layer (29).…”

Vasoactive intestinal polypeptide (VIP): Effect on rabbit uterine smooth muscle in vivo and in vitro

“…An excitatory effect of VIP has been reported in the small intestine (Kachelhoffer et al 1976, Cohen & Landry 1980 and bladder (Johns 1979). Some of these results may have been caused by contamination of the VIP with histamine (Said & Mutt 1970).…”

“…Some of these results may have been caused by contamination of the VIP with histamine (Said & Mutt 1970). or by the stimulation of cholinergic (Cohen & Landry 1980) or non-cholinergic excitatory fibers (Kachelhoffer et al 1976). In order to evaluate the involvement of other receptors the effect of VIP was investigated in the presence of the muscarinic receptor blocker, atropine, the aand P-adrenergic blocking agents, (phentolamine, propranolol).…”

Electrophysiology and morphology of vasoactive‐intestinal‐peptide‐immunoreactive neurones of the guinea‐pig ileum.

“…VIP is known to have powerful relaxant effects on many smooth muscles, including that of the gastrointestinal tract (Piper, Said & Vane, 1970;Kachelhoffer, Mendel, Dauchel, Hohmatter & Grenier, 1976), and it has been suggested that the peptide serves an important functional role as an inhibitory neurotransmitter (Fahrenkrug, Haglund, Jodal, Lundgren, Olbe & Schaffalitzky de Muckadell, 1978;. A long-standing, unanswered question concerns the identity of the final mediator of the descending inhibitory component of the peristaltic reflex (Hirst & McKirdy, 1974).…”