The importance of C‐terminal residues of vertebrate and invertebrate tachykinins for their contractile activities in gut tissues

Abstract

The C-terminal residues of mammalian tachykinins and urechistachykinins (Uru-TKs), tachykinin-related peptides of echiuroid worm origin, were substituted for each other. Their contractile effects were assayed on the cockroach hindgut and the guinea pig ileum. [Met 10 ] substitution of Uru-TKs caused a 1000 times lower activity on the hindgut, but a 1000 times higher activity on the ileum. In contrast, [Arg 11 ]substance P (SP) was 100 times more and 400 times less potent than SP on the hindgut and ileum, respectively. A SP antagonist blocked these Uru-TK activities on the hindgut. These results demonstrated that the C-terminal Met-NH 2 is necessary for ileum contraction and the Arg-NH 2 is required for hindgut contraction, which was caused by binding to the cockroach's neurokinin-like receptor.z 1999 Federation of European Biochemical Societies.

A novel tachykinin‐related peptide receptor

“…4A,B). These results are in good agreement with our previous study, showing that [Met10]Uru-TKs and SP failed to have any effect on the cockroach hindgut, while Uru-TKs exerted contractile activity [10,22]. In combination, these data confirmed that the presence of the -Arg-NH 2 residue in the Phe-X-Gly-Y-Arg-NH 2 consensus motif is critical for the activation of a tachykinin-related peptide receptor and that the binding site of tachykinin-related peptide receptors including UTKR discriminates between Arg-NH 2 and Met-NH 2 residues.…”

An Evolutionary Stress-Response Hypothesis for Chronic Widespread Pain (Fibromyalgia Syndrome)

“…So potent a stimulator of proinflammatory cytokines is the SP/NK1R pathway that one investigator wondered whether all inflammatory processes have “a requisite requirement for SP”[53]. Other defense‐ and repair‐related activities associated with the SP/NK1R pathway include: up‐regulation of “stress” hormones, such as norepinephrine and the precursors of cortisol, corticotropin‐releasing hormone and adrenal corticotrophic hormone [54]; down‐regulation of endogenous opioids such as met[hionine]‐enkephalin (MENK) [55,56] and other putative “feel‐good” neurotransmitters, such as serotonin [57]; stimulation of contraction and increased motility in the gut [58,59]; vomiting [60]; vasodilatation [61]; histamine release [62]; production [63] and migration [64] of new cells to damaged tissue; defensive alterations in cardiac [65] and respiratory [65] function; and edema following head injury [66].…”

Insight into Tachykinin-Related Peptides, Their Receptors, and Invertebrate Tachykinins: A review

“…The Uru-TK I and II analog, [Met 10 ]-Uru-TK I and II, in which the C-terminal Arg-NH 2 was substituted by Met-NH 2 , was shown to acquire the contractile activity on the guinea pig ileum to a similar degree to substance P, whereas authentic Uru-TK-I and II failed (Ikeda et al, 1999). Likewise, replacement of the Met-NH 2 with Arg-NH 2 in substance P, neurokinin A, and neurokinin B resulted in contraction of the cockroach hindgut and no effect on the guinea pig ileum (Ikeda et al, 1999).…”

“…The Uru-TK I and II analog, [Met 10 ]-Uru-TK I and II, in which the C-terminal Arg-NH 2 was substituted by Met-NH 2 , was shown to acquire the contractile activity on the guinea pig ileum to a similar degree to substance P, whereas authentic Uru-TK-I and II failed (Ikeda et al, 1999). Likewise, replacement of the Met-NH 2 with Arg-NH 2 in substance P, neurokinin A, and neurokinin B resulted in contraction of the cockroach hindgut and no effect on the guinea pig ileum (Ikeda et al, 1999). The competitive binding assay of NK1 for 125 I-labeled substance P also verified the binding activity of other Uru-TK analogs ([Met 10 ]-Uru-TKs III-V, and VII) to NK1 with almost equivalent potency to [Met 10 ]-Uru-TK I and II (Kawada et al, 2000).…”