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

Abstract

Peptide histidine isoleucine (PHI), peptide histidine valine (PHV), and vasoactive intestinal polypeptide (VIP) are cosynthesized from the same precursor and share high levels of structural similarities with overlapping biological functions. In this study, the first PHI/PHV receptor was isolated and characterized in goldfish. To study this receptor using homologous peptides, we have also characterized the goldfish prepro-PHI/VIP, and, surprisingly, a shorter transcript lacking the VIP coding region was isolated. A PHI/VIP precursor without the VIP coding sequence has never before been reported. peptide histidine isoleucine (PHI) are members of the pituitary adenylate cyclase-activating polypeptide (PACAP)/ glucagon family. These peptides share many structural and biological similarities. They are cosynthesized from a common precursor; colocalized in the central nervous, gastrointestinal, reproductive, and respiratory systems; and coreleased in response to stimulation (1-7). It is interesting to note that similar to PACAP-27 and PACAP-38, a C-terminally extended form of PHI, known as peptide histidine valine (PHV), is also present in high concentrations in the circulation (8), although the function of this peptide is still unclear.VIP and PHI mediate a number of similar physiological actions in many systems, but the potencies of PHI are one to three orders of magnitude lower than those of VIP in various studies (5, 9 -13). Thus, PHI has been considered a weak agonist for VIP. 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). In the vascular system, they produce an increase in vertebral artery blood flow (13).The biological effects of VIP are mediated through at least two receptor subtypes, termed VPAC1-R (16) and VPAC2-R (17), that exhibit high affinity for both VIP and PACAP. A third receptor, termed PAC1-R, that possesses high affinity for PACAP but a much lower affinity for VIP has been characterized (18). 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. However, there are examples indicating that the biological responses to PHI are distinct from those evoked by VIP: 1) PHI injection in the preoptic area of rats facilitates LH secretion, whereas VIP inj...

The serendipitous origin of chordate secretin peptide family members

“…VIP was isolated from cod ( Gadus morhua ) [39,40] and goldfish ( Carassius auratus ) [41], PACAP from the Japanese stargazer ( Uranoscopus japonicus ) [42] and GCG from the channel catfish ( Ictalurus punctatus ) [43,44] (Table 1). The identification of two transcripts for PHI/VIP in goldfish Carassius auratus [45] and zebrafish ( Danio rerio ) (PHI/VIP a , EU031789 and PHI/VIP b , EU031790) and of two PRP/PACAP (PRP/PACAP a , NM_152885 and PRP/PACAP b , AF329633) [46,47] and GCG/GLP precursors in zebrafish [48] suggests they are duplicates in fish and this has been confirmed by the identification of two PRP/PACAP and GCG/GLP genes in Takifugu (ENSTRUG00000003782 and ENSTRUG00000010059; ENSTRUG00000008721 and ENSTRUG00000004633, respectively) and Tetraodon (ENSTNIG00000017117 and ENSTNIG00000018649; ENSTNIG00000013278 and ENSTNIG00000000614, respectively) genomes (Table 2) [8]. The greater number of secretin family genes identified in fish relative to tetrapods is most likely to be a result of the proposed teleost specific genome duplication and the absence of GIP and GHRH gene duplicates suggests they were probably deleted [49-51].…”

Extreme Thermal Noxious Stimuli Induce Pain Responses in Zebrafish Larvae

“…In goldfish, the mRNA for vip is usually expressed in the brain and intestine (Tse et al, 2002). In zebrafish VIP is localized in nitrergic neurons and fibers of the neuro-enteric system (Olsson et al, 2008; Uyttebroek et al, 2010; Shepherd and Eisen, 2011).…”

“…These factors are involved in a variety of cellular processes including proliferation and survival, differentiation, growth, apoptosis, response to cell stress, cell migration and transformation (Loebrich and Nedivi 2009; Pérez-Cadahía et al, 2011). VIP is a potent peptide having many functions such as stimulating exocrine and endocrine secretion, moderating smooth muscle relaxation, regulating circadian rhythms and neuro-modulation (Tse et al, 2002). Nerve injury determines vip induction in dorsal root ganglia and dorsal horn of the spinal cord in rat (Ma and Bisby, 1998).…”

Excitatory actions of peptide histidine isoleucine on thalamic relay neurons

“…In addition to its own specific PHI receptor (Tse et al, 2002), PHI may act as a weak agonist on VIP receptors (Harmar et al, 1998;Gourlet et al, 1998;Palle et al, 1989;Inoue et al, 1988;Lundberg et al, 1984;Moriarty et al, 1984;Tapia-Arancibia and Reichlin, 1985;Yuwiler et al, 1993;Lutz et al, 1993). We next compared our current results of PHI-mediated depolarizations with our previously published results regarding VIP-mediated depolarizations of thalamic relay neurons (Lee and Cox, 2003).…”

“…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). …”