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| Targets |
Proctolin is an endogenous pentapeptide (Arg-Tyr-Leu-Pro-Thr) that acts as an excitatory neuromodulator in crustaceans and insects [1].
Its receptor is a G-protein coupled receptor (GPCR) [1]. |
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| ln Vitro |
Proctolin stimulates resting systems and raises action potential frequency and amplitude [1]. It also enhances muscular contraction amplitude. Proctolin functions as a neuromodulator and maybe a neurohormone in arthropods. It doesn't seem to perform like a conventional neurotransmitter [2]. The first insect neuropeptide to be chemically and sequence-characterized is proctolin, a pentapeptide containing the mature peptide RYLPT. CG7105 in Drosophila melanogaster was the first proctolin precursor gene to be identified. Even so, prior research indicated that B lacks proctolin. Mori, a proteomic investigation of B recently revealed the presence of this pentapeptide. mori wings. A similar gene was found in the Borer borer, but the Bombyx mori Proctolin gene does not provide mature peptides due to the absence of cleavage sites at the N- and C-termini of the RYLPT sequence. As a result, it is thought that neither Bombyx mori nor Borer borer have shown signs of having real Proctolin[3].
The physiological role of proctolin as a neuromodulator is well characterized. It can increase the frequency of action potentials, increase the amplitude of muscle contraction, and initiate activity in quiescent systems [1]. |
| ln Vivo |
In the American lobster Homarus americanus, three daily injections of proctolin to temporarily raise hemal concentrations to 10⁻⁶ M resulted in significant differential expression of 255 transcripts (adjusted p < 0.05) compared to saline-injected controls. Of these transcripts, 79 (31%) had reliable protein annotations [1].
Among the annotated transcripts, 80% were upregulated and largely included proteins involved in immune and neural systems. Neural transcripts included annexin, proteins involved in gap junctions between electrically connected neurons (adjusted p < 0.05, +3 log₂ fold change), and transient receptor potential channels (TRPA1, TRP pyrexia) (adjusted p < 0.05, +3 log₂ fold change) [1]. The greatest log₂ fold change was observed in three transcripts annotating to anti-lipopolysaccharide factors (ALFs) (adjusted p < 0.001, +5 log₂ fold change), which are peptides with potent anticoagulation and antimicrobial abilities. A stress-activated protein kinase identified in another crustacean immune response [UniprotKB: G0ZJ53] was also upregulated (adjusted p < 0.001, +4 log₂ fold change) [1]. These results indicate a relationship between hemal proctolin and increased synthesis of antimicrobial proteins, suggesting a novel role for proctolin in innate immunity pathways. This neuromodulator may be multi-faceted in its role as a signaling molecule, acting on both neural and immune systems [1]. |
| Animal Protocol |
Adult Homarus americanus were purchased from local commercial fisherman and held in ambient running seawater tanks (10.29 ± 0.01°C) at the Northeastern University Marine Science Center. Lobsters were not fed prior to experimentation [1].
Individuals were subjected to once-daily hormone treatments of proctolin (Arg-Tyr-Leu-Pro-Thr) for a three-day period. Proctolin was injected in physiological saline to temporarily increase systemic proctolin concentration to 10⁻⁶ M, based on standard hemolymph/bodyweight calculations and physiologically relevant concentration levels. Control treatments received physiological saline injections. The treatment period was selected based on time frames of ion channel turnover, a process that can take hours to days [1]. Efficacy of injections increasing systemic proctolin was confirmed by quantitative mass spectrometry [1]. Four different tissue types were collected from live Homarus americanus: (1) abdominal nerve cord (n = 3), (2) supraesophageal ganglion (the "brain") (n = 1), (3) heart and pericardial cavity with neurosecretory pericardial organ (n = 3), (4) muscle tissue from abdominal muscles (n = 3). Samples were removed with forceps and surgical scissors, flash-frozen in TRI reagent with liquid nitrogen, and pulverized with RNase-DNase-free pestles [1]. Adult Homarus americanus were purchased from local commercial fisherman and held in ambient running seawater tanks (10.29 ± 0.01°C) at the Northeastern University Marine Science Center. Lobsters were not fed prior to experimentation [1]. Individuals were subjected to once-daily hormone treatments of proctolin (Arg-Tyr-Leu-Pro-Thr) for a three-day period. Proctolin was injected in physiological saline to temporarily increase systemic proctolin concentration to 10⁻⁶ M, based on standard hemolymph/bodyweight calculations and physiologically relevant concentration levels. Control treatments received physiological saline injections. The treatment period was selected based on time frames of ion channel turnover, a process that can take hours to days [1]. Efficacy of injections increasing systemic proctolin was confirmed by quantitative mass spectrometry [1]. Four different tissue types were collected from live Homarus americanus: (1) abdominal nerve cord (n = 3), (2) supraesophageal ganglion (the "brain") (n = 1), (3) heart and pericardial cavity with neurosecretory pericardial organ (n = 3), (4) muscle tissue from abdominal muscles (n = 3). Samples were removed with forceps and surgical scissors, flash-frozen in TRI reagent with liquid nitrogen, and pulverized with RNase-DNase-free pestles [1]. |
| References | |
| Additional Infomation |
Proctolin are peptides.
Proctolin is an endogenous pentapeptide that acts as an excitatory neuromodulator. Its physiological role as a neuromodulator is well characterized in crustaceans and insects [1]. Proctolin can increase the frequency of action potentials, increase the amplitude of muscle contraction, and initiate activity in quiescent systems. It is also accepted to function at a system-wide hormonal level, a context in which this neuropeptide remains poorly understood [1]. The identified receptor for proctolin is a G-protein coupled receptor (GPCR), suggesting a mechanism by which proctolin may regulate various cellular responses through second messenger systems [1]. This study investigated the role of proctolin as a hormonal regulator of gene expression by treating lobsters with three daily exogenous proctolin injections to temporarily raise hemal concentrations. The results implicate a novel role for hemal proctolin in innate immunity pathways, suggesting this neuromodulator may be multi-faceted in its role as a signaling molecule and act on both neural and immune systems [1]. The upregulation of anti-lipopolysaccharide factors (ALFs) and stress-activated protein kinase in response to proctolin treatment indicates a relationship between this neuromodulator and increased synthesis of antimicrobial proteins, expanding our understanding of proctolin's physiological functions beyond neuromodulation [1]. |
| Exact Mass |
648.36
|
|---|---|
| CAS # |
57966-42-4
|
| PubChem CID |
123786
|
| Appearance |
White to off-white solid powder
|
| LogP |
2.832
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| Hydrogen Bond Donor Count |
9
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| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
17
|
| Heavy Atom Count |
46
|
| Complexity |
1080
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| Defined Atom Stereocenter Count |
6
|
| SMILES |
N/C(=N/CCCC(C(NC(C(NC(C(N1CCCC1C(NC(C(=O)O)C(O)C)=O)=O)CC(C)C)=O)CC1=CC=C(O)C=C1)=O)N)/N
|
| InChi Key |
KKUPPLMEDQDAJX-UEHMALFGSA-N
|
| InChi Code |
InChI=1S/C30H48N8O8/c1-16(2)14-22(28(44)38-13-5-7-23(38)27(43)37-24(17(3)39)29(45)46)36-26(42)21(15-18-8-10-19(40)11-9-18)35-25(41)20(31)6-4-12-34-30(32)33/h8-11,16-17,20-24,39-40H,4-7,12-15,31H2,1-3H3,(H,35,41)(H,36,42)(H,37,43)(H,45,46)(H4,32,33,34)/t17-,20+,21+,22+,23+,24+/m1/s1
|
| Chemical Name |
(2S,3R)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid
|
| Synonyms |
Gut factor Proctolin
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~154.14 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 100 mg/mL (154.14 mM) (saturation unknown) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution.
 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03366090 | UNKNOWN STATUS | Procedure: Biopsies during coloscopy | Crohn Disease IBD Immunological Profiles Immunology |
Rijnstate Hospital | 2017-10-01 | |
| NCT06495658 | RECRUITING | Dietary Supplement: Prebiotic | Crohn Disease Ulcerative Colitis |
University of California, Los Angeles | 2024-07-09 | Not Applicable |
| NCT00445627 | COMPLETED | Drug: Metformin Drug: Insulin Behavioral: Nutrition counseling Behavioral: Exercise counseling |
Diabetes Mellitus, Type 2 Obesity Overweight |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | 2007-06-18 |