EXPRESSION OF PREPRO-VIP DERIVED PEPTIDES IN THE GASTROINTESTINAL-TRACT OF NORMAL, HYPOTHYROID AND HYPERTHYROID RATS

Vasoactive intestinal polypeptide (VIP) is a widespread neuropeptide i nvolved in the autonomic nervous control of smooth muscle activity, bl ood flow and secretion. To study the biosynthetic processing of the VI P precursor in the gut of normal, hypo- and hyperthyroid rats we used antisera against the five functional domains of the precursor molecule , prepro-VIP 22-79, peptide histidine isoleucine (PHI), prepro-VIP 111 -122, VIP and prepro-VIP 156-170, to quantify and characterize VIP pre cursor peptides by radioimmunoassay and chromatography and examine the ir cellular localization and co-localization by immunohistochemistry. All five peptides were expressed in the gut but not in equimolar amoun ts as expected from the structure of the VIP precursor. A high concent ration of PHV, the C-terminally extended form of PHI which includes pr epro-VIP 111-122, was found in the small intestine. Immunohistochemica lly the prepro-VIP derived peptides were shown to coexist in neuronal elements. Changes in thyroid hormone status induced moderate changes i n peptide expression in the gut, the most prominent being a 2-fold inc rease in all prepro-VIP derived peptides in the gastric fundus of hypo thyroid rats. The findings indicate that differences in the post-trans lational processing of prepro-VIP exist in neurons of the rat gut and that hypo- and hyperthyroidism induce differential changes in peptide expression.