Kassinin

Last updated
Kassinin
Kassinin.png
Names
Other names
L-alpha-aspartyl-L-valyl-L-prolyl-L-lysyl-L-seryl-L-alpha-aspartyl-L-glutaminyl-L-phenylalanyl-L-valyl-glycyl-L-leucyl-L-methioninamide
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
MeSH Kassinin
PubChem CID
UNII
  • InChI=1S/C59H95N15O18S/c1-30(2)24-38(53(86)66-35(49(63)82)20-23-93-7)65-44(77)28-64-58(91)47(31(3)4)72-55(88)39(25-33-14-9-8-10-15-33)69-52(85)37(18-19-43(62)76)67-54(87)40(27-46(80)81)70-56(89)41(29-75)71-51(84)36(16-11-12-21-60)68-57(90)42-17-13-22-74(42)59(92)48(32(5)6)73-50(83)34(61)26-45(78)79/h8-10,14-15,30-32,34-42,47-48,75H,11-13,16-29,60-61H2,1-7H3,(H2,62,76)(H2,63,82)(H,64,91)(H,65,77)(H,66,86)(H,67,87)(H,68,90)(H,69,85)(H,70,89)(H,71,84)(H,72,88)(H,73,83)(H,78,79)(H,80,81)/t34-,35-,36-,37-,38-,39-,40-,41-,42-,47-,48-/m0/s1 X mark.svgN
    Key: NXTPETCPVNEEOP-FJCMUPJRSA-N X mark.svgN
  • CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N)NC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)N
Properties
C59H95N15O18S
Molar mass 1334.54
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Kassinin is a peptide derived from the Kassina frog. [1] It belongs to tachykinin family of neuropeptides. It is secreted as a defense response, and is involved in neuropeptide signalling. [2]

Contents

The amino acid sequence is H-Asp-Val-Pro-Lys-Ser-Asp-Gln-Phe-Val-Gly-Leu-Met-NH2 (DVPKSDQFVGLM-NH2).

Ion transportation

In frog skin, tachykinins are responsible for ion transportation. [3] Kassinin is one of the tachykinin peptides, which interacts with NK2 receptor to increase short circuit current (SCC), resulting in an ion transportation in frog skin. Another peptide that belongs to tachykinin family is Eledoisin that interacts with NK3 receptor for stimulation of SCC, but can be reduced by either NK1 or NK2 antagonist, whereas kassinin can't be reduced by either of these NK1, NK2 or NK3 antagonists. Kassinin is very effective in increasing short circuit current to its maximum within 10 minutes with increase of 26.13 ± 1.53 μΑ/cm2. [4]

There are some requirements that must be accomplished to gain short circuit stimulation. One of them is to have Phe-X-Gly-Leu-Met-NH2 sequence at C-terminal where X could be Val or Ile. The other requirement is to have 2 or 1 proline residue at N-terminal. [3] If only one proline residue is present, then there must be one basic amino acid present in the sequence. For instance kassinin has one proline residue and one basic amino acid (Lys). Another example would be of enterokassinin that does have one proline reside but doesn't have any basic amino acid in the sequence. Thus it doesn't increase SCC and therefore is ineffective in ion transportation. [4] While kassinin plays an effiecient role in ion transportation in frog skin.

Tachykinins

Study of amphibious kassinin has allowed breakthrough discoveries of mammalian tachykinins. Substance P (SP) was originally considered the only neuropeptide in mammals capable of neuromodulation, with the X position of the carboxyl sequence typical for these polypeptides having a Phe residue. [5] In 1983, two neuropeptides with X = Val were discovered from bovine spinal serum, and bioassays to test for the measured synaptic response and their inhibition by known antagonists revealed that this was a novel discovery that differed from SP. Previously, mammalian receptors were only thought to be specific to SP and divided into SP-P and SP-E receptors, the latter of which was much more potent (approximately 10-100 fold) in response and named after Eledoisin which was non-mammalian. Testing the hypothesis that SP-E receptors were potent because they must have another ligand of greater specificity led to the discovery of the aforementioned novel neuropeptides. Aptly named Substake K (SK) and neuromedin K (NMK) due to structural homology with kassinin, the pharmacological effects also establish these as major player in mammalian systems, with SK having only 1/3rd the effect on SP-P specific receptors while SP-E receptors in rat vas deferense experienced a 300x greater effect upon binding SK. With only 3 tachykinins having been studied, it was the study of kassinin that allowed these emprical comparisons to be made. [6]

As a research tool

Novel discovery of new mammalian tachykinins similar to amphibian Kasshinin led to an interest in postulating kassinin's direct action on mammalian CNS. Kassinin injections administered to rats upon subjecting their cells to dehydration due to high salt content, led to the discovery that the neuropeptide inhibits thirst despite the cellular dehydration for up to several hours. Throughout the duration of study, sodium excreted through urine is also low in concentration, and given that the amount of water intake after 6 hours is not sufficient to restore osmotic balance, scientists hypothesize that kassinin triggers an osmotic exchange between intra and intercellular components to maintain water potential. Whether this is due to a CNS modification in the homeostatic regulation of cecllular osmosis is undetermined. [7]

While kassinin is not synthesized in the human CNS nad PNS, it has been reported via exposure to external elements and can hence be considered a component of the human exposome, [8] which, given the greater extent of homology in human and rate genome justified to growing interest in the neuropeptide.

Related Research Articles

<span class="mw-page-title-main">Substance P</span> Chemical compound

Substance P (SP) is an undecapeptide and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its closely related neurokinin A (NKA) are produced from a polyprotein precursor after differential splicing of the preprotachykinin A gene. The deduced amino acid sequence of substance P is as follows:

<i>beta</i>-Endorphin Peptide hormone in humans

beta-Endorphin (β-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin.

<span class="mw-page-title-main">Dermorphin</span> Chemical compound

Dermorphin is a hepta-peptide first isolated from the skin of South American frogs belonging to the genus Phyllomedusa. The peptide is a natural opioid that binds as an agonist with high potency and selectivity to mu opioid receptors. Dermorphin is about 30–40 times more potent than morphine, but theoretically may be less likely to produce drug tolerance and addiction due to its high potency. The amino acid sequence of dermorphin is H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2.

<span class="mw-page-title-main">FMRFamide</span> Chemical compound

FMRFamide (H-Phe-Met-Arg-Phe-NH2) is a neuropeptide from a broad family of FMRFamide-related peptides (FaRPs) all sharing an -RFamide sequence at their C-terminus. First identified in Hard clam, it is thought to play an important role in cardiac activity regulation. Several FMRFamide related peptides are known, regulating various cellular functions and possessing pharmacological actions, such as anti-opiate effects. In Mercenaria mercenaria, FMRFamide has been isolated and demonstrated to increase both the force and frequency of the heartbeat through a biochemical pathway that is thought to involve the increase of cytoplasmic cAMP in the ventricular region.

<span class="mw-page-title-main">Tachykinin peptides</span>

Tachykinin peptides are one of the largest families of neuropeptides, found from amphibians to mammals. They were so named due to their ability to rapidly induce contraction of gut tissue. The tachykinin family is characterized by a common C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is either an Aromatic or an Aliphatic amino acid. The genes that produce tachykinins encode precursor proteins called preprotachykinins, which are chopped apart into smaller peptides by posttranslational proteolytic processing. The genes also code for multiple splice forms that are made up of different sets of peptides.

<i>Kassina</i> Genus of amphibians

Kassina is a genus of hyperoliid frogs, commonly referred to as running frogs or kassinas. They are found throughout sub-Saharan Africa. They are characterized by preferring a distinctive "walking" with the back legs instead of the more traditional frog-hopping.

Physalaemin is a tachykinin peptide obtained from the Physalaemus frog, closely related to substance P. Its structure was first elucidated in 1964.

<span class="mw-page-title-main">Corticotropin-like intermediate peptide</span> Chemical compound

Corticotropin-like intermediate [lobe] peptide (CLIP), also known as adrenocorticotropic hormone fragment 18-39, is a naturally occurring, endogenous neuropeptide with a docosapeptide structure and the amino acid sequence Arg-Pro-Val-Lys-Val-Tyr-Pro-Asn-Gly-Ala-Glu-Asp-Glu-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe. CLIP is generated as a proteolyic cleavage product of adrenocorticotropic hormone (ACTH), which in turn is a cleavage product of proopiomelanocortin (POMC). Its physiological role has been investigated in various tissues, specifically in the central nervous system.

Neurokinin 1 (NK1) antagonists (-pitants) are a novel class of medications that possesses unique antidepressant, anxiolytic, and antiemetic properties. NK-1 antagonists boost the efficacy of 5-HT3 antagonists to prevent nausea and vomiting. The discovery of neurokinin 1 (NK1) receptor antagonists was a turning point in the prevention of nausea and vomiting associated with cancer chemotherapy.

<span class="mw-page-title-main">Neurokinin A</span> Chemical compound

Neurokinin A (NKA), formerly known as Substance K, is a neurologically active peptide translated from the pre-protachykinin gene. Neurokinin A has many excitatory effects on mammalian nervous systems and is also influential on the mammalian inflammatory and pain responses.

<span class="mw-page-title-main">Tachykinin receptor 1</span> Protein-coding gene in the species Homo sapiens

The tachykinin receptor 1 (TACR1) also known as neurokinin 1 receptor (NK1R) or substance P receptor (SPR) is a G protein coupled receptor found in the central nervous system and peripheral nervous system. The endogenous ligand for this receptor is Substance P, although it has some affinity for other tachykinins. The protein is the product of the TACR1 gene.

<span class="mw-page-title-main">Dynorphin B</span> Chemical compound

Dynorphin B, also known as rimorphin, is a form of dynorphin and an endogenous opioid peptide with the amino acid sequence Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr. Dynorphin B is generated as a proteolytic cleavage product of leumorphin, which in turn is a cleavage product of preproenkephalin B (prodynorphin).

<span class="mw-page-title-main">Tachykinin receptor 2</span> Protein-coding gene in the species Homo sapiens

Substance-K receptor is a protein that in humans is encoded by the TACR2 gene.

<span class="mw-page-title-main">Tachykinin receptor 3</span> Protein-coding gene in the species Homo sapiens

Tachykinin receptor 3, also known as TACR3, is a protein which in humans is encoded by the TACR3 gene.

<span class="mw-page-title-main">Eledoisin</span> Chemical compound

Eledoisin is an undecapeptide of mollusk origin, belonging to the tachykinin family of neuropeptides.

<span class="mw-page-title-main">TAC3</span> Protein-coding gene in the species Homo sapiens

Tachykinin-3 is a protein that in humans is encoded by the TAC3 gene.

RVD-Hpα (pepcan-12) is an endogenous neuropeptide found in human and mammalian brain, which was originally proposed to act as a selective agonist for the CB1 cannabinoid receptor. It is a 12-amino acid polypeptide having the amino acid sequence Arg-Val-Asp-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His and is an N-terminal extended form of hemopressin, a 9-AA polypeptide derived from the α1 subunit of hemoglobin which has previously been shown to act as a CB1 inverse agonist. All three polypeptides have been isolated from various mammalian species, with RVD-Hpα being one of the more abundant neuropeptides expressed in mouse brain, and these neuropeptides represent a new avenue for cannabinoid research distinct from the previously known endogenous lipid-derived cannabinoid agonists such as anandamide. Recently it was shown that RVD-Hpα (also called Pepcan-12) is a potent negative allosteric modulator at CB1 receptors, together with other newly described N-terminally extended peptides (pepcans).

<i>alpha</i>-Endorphin Chemical compound

alpha-Endorphin (α-Endorphin) is an endogenous opioid peptide with a length of 16 amino acids, and the amino acid sequence: Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr. With the use of mass spectrometry, Nicholas Ling was able to determine the primary sequence of a-endorphin.

Deltorphin, also known as deltorphin A and dermenkephalin, is a naturally occurring, exogenous opioid heptapeptide and thus, exorphin, with the amino acid sequence Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2. Along with the other deltorphins (such as deltorphin I and deltorphin II) and the dermorphins, deltorphin is endogenous to frogs of the genus Phyllomedusa such as P. bicolor and P. sauvagei where it is produced in their skin, and is not known to occur naturally in any other species. Deltorphin is one of the highest affinity and most selective naturally occurring opioid peptides known, acting as a very potent and highly specific agonist of the δ-opioid receptor.

Sauvagine is a neuropeptide from the corticotropin-releasing factor (CRF) family of peptides and is orthologous to the mammalian hormone, urocortin 1, and the teleost fish hormone, urotensin 1. It is 40 amino acids in length, and has the sequence XGPPISIDLSLELLRKMIEIEKQEKEKQQAANNRLLLDTI-NH2, with a pyrrolidone carboxylic acid modification at the N-terminal and amidation of the C-terminal isoleucine residue. It was originally isolated from the skin of the frog Phyllomedusa sauvagii. Given its relation to other CRF-related peptides, it exerts similar physiological effects as corticotropin-releasing hormone.

References

  1. ↑ Anastasi A, Montecucchi P, Erspamer V, Visser J (July 1977). "Amino acid composition and sequence of kassinin, a tachykinin dodecapeptide from the skin of the African frog Kassina senegalensis". Experientia. 33 (7): 857–858. doi:10.1007/bf01951242. PMID   891753. S2CID   19421025.
  2. ↑ "Kassinin". UniProt.
  3. 1 2 Lippe C, Lobasso S, Cassano G, Bellantuono V, Ardizzone C (1998-01-01). "Actions of tachykinins on the ion transport across the frog skin". Peptides. 19 (8): 1435–1438. doi:10.1016/S0196-9781(98)00080-1. PMID   9809659. S2CID   33378999.
  4. 1 2 Lippe C, Bellantuono V, Ardizzone C, Cassano G (November 2004). "Eledoisin and Kassinin, but not Enterokassinin, stimulate ion transport in frog skin". Peptides. 25 (11): 1971–1975. doi:10.1016/j.peptides.2004.06.014. PMID   15501529. S2CID   42684110.
  5. ↑ Simmons MA (2010). "Substance P". xPharm: The Comprehensive Pharmacology Reference. pp. 1–4. doi:10.1016/B978-008055232-3.63935-2. ISBN   9780080552323.
  6. ↑ Maggio JE (1985-01-01). ""Kassinin" in mammals: the newest tachykinins". Peptides. 6 Suppl 3: 237–243. doi:10.1016/0196-9781(85)90380-8. PMID   2421262. S2CID   20966612.
  7. ↑ M., Perfumi; G., do Caro; I., Panocka; C., Polidori; M., Massi (1988-12-01). "Effects of kassinin, a tachykinin of the skin of the African frog Kassina senegalensis, on body fluid homeostasis in rats". Pharmacological Research Communications. 20: 67–70. doi:10.1016/S0031-6989(88)80843-9. ISSN   0031-6989. PMID   3247356.
  8. ↑ "Human Metabolome Database: Showing metabocard for Kassinin (HMDB0253764)". hmdb.ca. Retrieved 2021-11-30.
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