Commonalities in vasoactive intestinal peptide and peptide N‐terminal histidine C‐terminal isoleucine stimulation of N‐acetyltransferase activity in the rat pineal

Abstract

Exposure of adult rat pineal glands in organ culture to the polypeptides vasoactive intestinal polypeptide (VIP), and peptide N-terminal histidine C-terminal isoleucine (PHI) increases pineal serotonin N-acetyltransferase (NAT) activity and melatonin synthesis. The following research results are taken to indicate that VIP and PHI share common components of the NAT induction system: (1) The effects of the two peptides are additive at concentrations of 10 nM VIP and 100 nM PHI but not at higher peptide concentrations. (2) Pineals from newborns also respond to PHI with a dose dependent increase in NAT activity. NAT responses are additive at the same concentrations as seen with the adult pineals. (3) Light exposure affects the sensitivity of pineals to VIP and PHI stimulation in a similar manner; pineals taken after 3 hr of light are much less sensitive to PHI or VIP than those taken after 13 hr of light. (4) Pineals exposed for 48 hr to either PHI or VIP have a reduced NAT response to either agonist, which is reversible by culture in agonist-free media. (5) Neither VIP nor PHI stimulation of NAT activity is affected by concentrations of the VIP antagonists (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 (NAcTDGRF), L-8-K, VIP-Neurotensin Hybrid (VIPNET), or (4Cl-D-Phe6, Leu17)-VIP (4C1PLVIP), which affect VIP binding or function in other tissues.

Identification of a Potential Receptor for Both Peptide Histidine Isoleucine and Peptide Histidine Valine

“…The pattern of distribution of PHI/VIP precursors is similar to that reported in humans (50). In the central nervous system, VIP and PHI stimulate somatostatin release (10) and increase melatonin synthesis in the rat pineal (12). In fish, VIP inhibits gastric acid secretion and reduces gastric mucosal blood flow in cod (51).…”

“…In the gastrointestinal system, they both augment water and electrolyte transport in the jejunum (9,14) and glucagon release from the pancreas (15). In the neuroendocrine system, they stimulate the secretion of PRL in the pituitary (10) and increase melatonin synthesis in the pineal gland (12). In the reproductive system, both peptides inhibit fallopian smooth muscle activity (5).…”

“…Up to now, a selective PHI receptor has not been identified, and it was generally accepted that the effects of PHI were mediated through VIP receptors. As a matter of fact, there is evidence that PHI shares common receptors with VIP: 1) PHI has been reported to bind VIP-preferring sites in many preparations (19 -21); 2) maximal doses of PHI and VIP do not produce additive effects (5, 10 -13, 16); and 3) cross-desensitization of PHI and VIP has been demonstrated (11,12,21). Thus, it is likely that at least some of the actions of PHI are mediated by binding to VIP-preferring sites.…”

Excitatory actions of peptide histidine isoleucine on thalamic relay neurons

“…PHI has been described as a weak agonist for both VPAC 1 and VPAC 2 receptors (Harmar et al, 1998;Palle et al, 1989;Inoue et al, 1988;Lundberg et al, 1984;Tapia-Arancibia and Reichlin, 1985;Lutz et al, 1993;Gourlet et al, 1998;Moriarty et al, 1984;Yuwiler et al, 1993). More recently, an independent PHI receptor has been cloned and characterized in fish; however, the existence of this receptor in mammals is still unknown (Tse et al, 2002).…”

Effect of peptide histidine isoleucine on consummatory behavior in rats

“…PHI, VIP, peptide histidine valine (PHV), and peptide histidine methionine, among others, are processed from this precursor molecule. Prepro-VIPrelated peptides, including PHI, share a structural homology, as well as a certain degree of functional similarities, e.g., by having a stimulatory effect on the release and/or synthesis of glucagon (8), prolactin (20,28,40), and melatonin (21,37,49), and by affecting circadian rhythmicity (2,3), heart rate (38), vasomotor functions (15,19), and activation of the hypothalamic-pituitaryadrenal (HPA) axis (4,6).…”