Bobbie J. Chrysanthou

Purification and characterisation of cerebellins from human and porcine cerebellum

The primary human and porcine structure of the novel neuropeptide cerebellin is unknown. These peptides were, therefore, isolated by a combination of ion‐exchange and reverse‐phase chromatography using a specific radioimmunoassay against rat cerebellin. The sequences of the peptides were deduced by mass spectrometry (for both human and porcine cerebellins) and gas‐phase Edman degradation (for porcine cerebellin). In both species, two molecular forms were identified. In the human, the major form corresponded to the pentadecamer [des‐Ser1]‐cerebellin (˜95% of the total) and the minor form, to the hexadecamer peptide. In the pig. however, both molecular forms were present in approximately equal amounts. The finding that the sequences of human and porcine cerebellin are identical to that of the rat suggests that strong evolutionary pressure has acted to conserve this sequence.

Effects of Prepro-Vasoactive Intestinal Polypeptide-Derived Peptides on Net Fluid Flux in Small Intestine of Anesthetized Rats

Intravenous infusion of low doses of vasoactive intestinal polypeptide, peptide histidine valine-42, and peptide histidine methionine (and the rat equivalent, peptide histidine isoleucine) into anesthetized rats caused a reduction in net absorption of fluid from the small intestine. Larger doses caused a net fluid secretion. At the same nominal infusion rates, peptide histidine valine-42 appeared to be the most potent. In terms of plasma concentrations achieved, however, vasoactive intestinal polypeptide was approximately six times more active than the other two human peptides. If confirmed in humans, these results would suggest that peptide histidine methionine and peptide histidine valine may be as important as vasoactive intestinal polypeptide in causing the watery diarrhea seen in the Verner-Morrison syndrome in which plasma levels of all three peptides are raised.

Infusion of prepro-VIP derived peptides in man: effect on secretion of prolactin.

Infusion of the three human prepro-VIP derived peptides [vasoactive intestinal peptide (VIP), peptide histidine methionine (PHM) and the newly discovered peptide histidine valine (PHV-42)] at a constant nominal rate of 5 pmol/kg/min in 6 healthy volunteers for 60 min resulted in plateau plasma levels of 56,475 and 1,052 pmol/l, respectively. Although these values were above those found in the circulation under physiological conditions, only VIP caused a significant rise of prolactin (PRL) during, and postinfusion. Circulating luteinizing hormone and cortisol concentrations remained unchanged. As peptide histidine isoleucine, the porcine equivalent of PHM, has been postulated to be a potent hypophyseal portal pituitary PRL-releasing factor in the rat, we suggest that in man, VIP is more active than either PHM or PHV-42, and is likely to be a better candidate.

Effects of preprovasoactive intestinal polypeptide-derived peptides on ileal output

Tumors associated with the Verner Morrison syndrome secrete peptide histidine methionine, its C-terminally extended variant peptide histidine valine, and vasoactive intestinal peptide. There is evidence that vasoactive intestinal peptide mediates diarrhea, but recent evidence suggested that peptide histidine methionine and peptide histidine valine may be at least as important. Infusion of vasoactive intestinal peptide, peptide histidine methionine, and peptide histidine valine into patients with ileostomies produced mean plateau plasma levels of 163, 1301, and 2106 pM, respectively, which are within the range seen in the Verner Morrison syndrome. Vasoactive intestinal peptide produced an integrated ileal output of 174 (53) g (mean [SEM]), compared with only 20 (7) g with peptide histidine methionine and 10 (3) g with peptide histidine valine. These results suggest that vasoactive intestinal peptide is substantially more important than peptide histidine methionine or peptide histidine valine in mediating diarrhea in the Verner Morrison syndrome.

Peptide histidine valine-42 stimulates gastric acid secretion in man

The effect of peptide histidine valine-42 (PHV-42) on gastric acid secretion was studied in man. PHV-42 was infused into 5 healthy volunteers at a dose of 10 pmol/kg/min. This dose caused a significant stimulation of basal gastric acid and potassium output. there were no significant changes in circulating gastrin throughout the infusion. In 2 subjects with a background of submaximal pentagastrin stimulation, PHV-42 infusion at the same dose did not alter acid secretion in either subject. The previous observation that PHV-42 is found particularly in the stomach and the new finding that it stimulates basal gastric secretion suggest the possibility that PHV-42 could have a role in local control of acid secretion.

Peptide histidine methionine (PHM) increases ileostomy output

The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PHM) which has substantial sequence homology with VIP. Both are present in nerve fibers in the human ileum and circulate in greatly increased concentrations in patients with the watery diarrhoea syndrome. We have infused PHM (23 pmol/kg/min) into 5 patients with ileostomies to determine the effect of PHM on human ileal output. Plasma PHM levels rose from 22 +/- 6 to 6013 +/- 874 pM (mean +/- S.E.M.) during PHM infusions and ileal output rose from 16 +/- 3 to 177 +/- 27 g/30 min (P less than 0.0001). PHM infusions also produced a significant fall in the percentage of solid material and a rise in the concentration of chloride in the ileal effluent. Mean plasma PHM concentrations during PHM infusions were equal to the highest levels seen in patients with the watery diarrhoea syndrome, so PHM may contribute to diarrhoea in this condition. Neuronal PHM may exert physiological control over ileal transport of water and electrolytes.