Peptide PHI, also known as peptide histidine isoleucine, is a peptide which functions as a hormone. This peptide contains a composition of 27 amino acids with histidine on the N-terminus and isoleucine on the C-terminus. It was originally isolated from mammalian small intestine amongst mammalian neurons called intramural neurons which function in motor activity of the intestinal walls.[1] An example of this was revealed in a study that demonstrated that this peptide regulates water and electrolyte transportation in the human jejunum; similar to its inhibitory effects on fluid absorption in the small intestine of pigs and rats.[2]

Rat Peptide histidine isoleucine (PHI) structure

Peptide histidine isoleucine (PHI) is part of family that plays a vital role in the cell growth rate such as in the intestine as well as in brain.[3] It was derived from glucagon family called the pituitary adenylate cyclase-activating polypeptide (PACAP) and it has an amino acid sequence homology to vasoactive intestinal peptide, secretin, glucagon, and other growth hormone releasing factor.[4] Human studies have shown that the release of PHI into the stomach regulates the neuroendocrine cell processes that affect gastrointestinal physiology. This peptide is present within the central nervous system that help regulate food consumption behavior, while at peripheral nervous system this peptide accumulates in the stomach which controls the digestion of food.[5]

It also plays a role in the regulation of prolactin in humans.[6] It functions specifically function in the G protein signaling pathway through G protein, which is a transmembrane protein that causes the cascade phosphorylation. It is located throughout the entire length of intestine while PHI is mostly concentrated in the colon region.[7]


  1. ^ Curro, Diego; Preziosi, Paolo; Ragazzoni, Enzo; Ciabattoni, Giovanni (1994). "Peptide histidine isoleucine-like immunoreactivity release from the rat gastric fundus". British Journal of Pharmacology. 113 (2): 541–549. doi:10.1111/j.1476-5381.1994.tb17023.x. PMC 1510139. PMID 7834206.
  2. ^ Moriarty, K; Hegarty, J; Tatemoto, K; Mutt, V; Christofides, N; Bloom, S; Wood, J (June 1, 1984). "Effect of peptide histidine isoleucine on water and electrolyte transport in the human jejunum". Gut. 25 (6): 624–628. doi:10.1136/gut.25.6.624. PMC 1432383. PMID 6547400.
  3. ^ Tatemoto, Kazuhiko; Mutt, Viktor (June 1980). "Isolation of two novel candidate hormones using a chemical method for finding naturally occurring polypeptides". Nature. 285 (5764): 417–418. doi:10.1038/285417a0. ISSN 1476-4687. PMID 6892950. S2CID 4262014.
  4. ^ Lelièvre, Vincent; Pineau, Nicolas; Du, Joanna; Wen, Chia-Hui; Nguyen, Thinh; Janet, Thierry; Muller, Jean-Marc; Waschek, James A. (1998-07-31). "Differential Effects of Peptide Histidine Isoleucine (PHI) and Related Peptides on Stimulation and Suppression of Neuroblastoma Cell Proliferation: A NOVEL VIP-INDEPENDENT ACTION OF PHI VIA MAP KINASE". Journal of Biological Chemistry. 273 (31): 19685–19690. doi:10.1074/jbc.273.31.19685. ISSN 0021-9258. PMID 9677397.
  5. ^ Olszewski, Pawel; Wirth, Michelle; Shaw, Timothy; Grace, Martha; Levine, Allen (February 20, 2003). "Peptides that Regulate Food Intake Effect of peptide histidine isoleucine on consummatory behavior in rats". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 284 (6): R1445–R1453. doi:10.1152/ajpregu.00554.2002. PMID 12595279.
  6. ^ Kulick R, Chaiseha Y, Kang S, Rozenboim I, El Halawani M (2005). "The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey". Gen Comp Endocrinol. 142 (3): 267–273. doi:10.1016/j.ygcen.2004.12.024. PMID 15935152.
  7. ^ Yiangou, Y.; Christofides, N.D.; Blank, M.A.; Yanaihara, N.; Tatemoto, K.; Bishop, A.E.; Polak, J.M.; Bloom, S.R. (September 1985). "Molecular forms of peptide histidine isoleucine-like immunoreactivity in the gastrointestinal tract". Gastroenterology. 89 (3): 516–524. doi:10.1016/0016-5085(85)90445-7. ISSN 0016-5085. PMID 3839480.

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