Vasoactive intestinal peptide (VIP).

Abstract

In 1969, Said and Mutt reported the extraction from secretion, increased flow of alkaline pancreatic normal lung tissue of a peptide which was capable juice and small intestinal juice with increased cyclic of causing gradual but prolonged peripheral AMP content (Makhlouf and Said, 1975), overlap vasodilation. This finding led them to search for markedly with the actions of the other three peptides. similar vasoactive substances in extracts of other Thus VIP was included as a member of the secretin metabolically active organs and, in 1970, they family ofhormonal peptides and, in 1974, it appeared described the isolation of a potent peripheral and in a list of 'candidate hormones of the gut' compiled splanchnic vasodilatory peptide from hog small by Grossman et al. (1974). intestine, which they named Vasoactive Intestinal In the eight or so years since its discovery, a great Peptide (VIP) (Said and Mutt, 1970 a, b). Subsequent deal of information has been amassed about VIP. purification of VIP allowed determination of its With the development of highly sensitive and specific amino-acid sequence, which showed it to be a radioimmunoassays for VIP, it has been possible to straight chain of 28 amino-acid residues with basic study its distribution in the body and its mode of properties because of a predominance of arginine release. However, with this growth in knowledge and lysine residues (Said and Mutt, 1972). Comparicontroversy developed as to whether VIP fulfilled son of the amino-acid sequence of VIP with those of the classical criteria for a hormone or whether it the classical hormones secretin and pancreatic acted locally as a paracrine substance or even as a glucagon showed a considerable degree of homology neurotransmitter or neuromodulatory substance. (Fig. 1). Thus, these three peptides, together with the This has now been resolved in favour of the latter, more recently discovered glucose-dependent insulin as discussed below. releasing polypeptide (GIP), were thought to be Perhaps one of the first indications that VIP related and it was suggested that they were perhaps might not be a hormone was obtained -from its derived from a common ancestral peptide. Further distribution in the gut. Unlike the other members of weight was added to these suggestions by the fact the secretin family, which are located in discrete that the many biological effects of VIP, which regions of the upper small intestine (secretin) and include systemic vasodilation, glycogenolysis (Kerins pancreas (glucagon), VIP appeared to have a much and Said, 1973), lipolysis (Frandsen and Moody, wider distribution. High concentrations of VIP were' 1973), inhibition of gastric acid production found throughout the length of the gut from the (Makhlouf and Said, 1975), stimulation of oesophagus to the rectum, including the pancreas myocardial contractility (Said et al., 1972), insulin (Bloom et al., 1975; Said, 1975) (Fig. 2). A similar *Serum is [unsuitable for VIP estimations as the level falls distribution of VIP-producing endocrine cells was during the time taken for the clot to form and retract. also observed by some authors (Polak et al., 1974; Plasma should be frozen immediately after collection-Ed. Buffa et al., 1977) (Fig. 2). Others, however, (Larsson