scholarly journals Discovery of Novel Caeridins from the Skin Secretion of the Australian White’s Tree Frog, Litoria caerulea

2018 ◽  
Vol 2018 ◽  
pp. 1-18
Author(s):  
Lei Li ◽  
Qing Wu ◽  
Xi Wang ◽  
Huimin Lu ◽  
Xinping Xi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Drug Discovery ◽  
Frog Skin ◽  
Smooth Muscles ◽  
Biologically Active ◽  
Tree Frog ◽  
Skin Secretion ◽  
Bladder Smooth Muscle ◽  
Gram Positive Bacteria ◽  
Litoria Caerulea

Abundant biologically active peptides have been discovered from frog skin secretions, a rich natural source of bioactive compounds with great potential in drug discovery. In this study, three Caeridin peptides, namely, Caeridin-1, S5-Caeridin-1, and Caeridin-a1, were discovered from the skin secretion of the Australian White’s tree frog, Litoria caerulea, for the first time, by means of combining transcriptomic and peptidomic analyses. It also represents the first report on bioactive Caeridins since this family of peptides was initially studied 20 years ago. Chemically synthetic versions of each natural Caeridin demonstrated promising bioactivities either on rat smooth muscles or against microbial growth. Specifically, Caeridin-1 produced contraction of rat bladder smooth muscle, while S5-Caeridin-1 induced relaxation of rat ileum smooth muscle, both at nanomolar concentrations. Moreover, Caeridin-a1 was shown to potently inhibit the growth of the planktonic Gram-positive bacteria Staphylococcus aureus (S. aureus), methicillin-resistant S. aureus (MRSA), and Enterococcus faecalis (E. faecalis), the Gram-negative bacterium, Escherichia coli (E. coli), and the yeast, Candida albicans (C. albicans). The discovery of these Caeridins may induce further intensive and systematic studies of frog skin peptides to promote the discovery of natural templates as lead compounds for drug discovery and therapeutic application.

Regional variation in myosin isoforms and phosphorylation at the resting tone in urinary bladder smooth muscle

2001 ◽  
Vol 280 (2) ◽  
pp. C254-C264 ◽  
Author(s):  
Joseph A. Hypolite ◽  
Michael E. DiSanto ◽  
Yongmu Zheng ◽  
Shaohua Chang ◽  
Alan J. Wein ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Smooth Muscles ◽  
Urinary Continence ◽  
Myosin Isoforms ◽  
Bladder Smooth Muscle ◽  
Rt Pcr ◽  
Total Rna ◽  
Bladder Dome ◽  
Significant Difference

Urinary bladder filling and emptying requires coordinated control of bladder body and urethral smooth muscles. Bladder dome, midbladder, base, and urethra showed significant differences in the percentage of 20-kDa myosin light chain (LC20) phosphorylation (35.45 ± 4.6, 24.7 ± 2.2, 13.6± 2.1, and 12.8 ± 2.7%, respectively) in resting muscle. Agonist-mediated force was associated with a rise in LC20 phosphorylation, but the extent of phosphorylation at all levels of force was less for urethral than for bladder body smooth muscle. RT-PCR and quantitative competitive RT-PCR analyses of total RNA from bladder body and urethral smooth muscles revealed only a slight difference in myosin heavy chain mRNA copy number per total RNA, whereas mRNA copy numbers for NH2-terminal isoforms SM-B (inserted) and SM-A (noninserted) in these muscles showed a significant difference (2.28 × 108 vs. 1.68 × 108 for SM-B and 0.12 × 108 vs. 0.42 × 108 for SM-A, respectively), which was also evident at the protein level. The ratio of COOH-terminal isoforms SM2:SM1 in the urethra was moderately but significantly lower than that in other regions of the bladder body. A high degree of LC20phosphorylation and SM-B in the bladder body may help to facilitate fast cross-bridge cycling and force generation required for rapid emptying, whereas a lower level of LC20 phosphorylation and the presence of a higher amount of SM-A in urethral smooth muscle may help to maintain the high basal tone of urethra, required for urinary continence.

Ca2+ channel antagonist actions in bladder smooth muscle: comparative pharmacologic and [3H]nitrendipine binding studies

1985 ◽  
Vol 63 (5) ◽  
pp. 453-462 ◽  
Author(s):  
F. B. Yousif ◽  
G. T. Bolger ◽  
A. Ruzycky ◽  
D. J. Triggle
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Affinity Binding ◽  
Induced Responses ◽  
Bladder Smooth Muscle ◽  
Binding Studies ◽  
Tonic Component ◽  
High Affinity Binding ◽  
High Affinity

The actions of a series of 15 Ca2+ channel antagonists including D-6(X), nifedipine, and diltiazem were examined against K+ depolarization and muscarinic receptor induced responses in guinea pig bladder smooth muscle. Responses of bladder are very dependent upon extracellular Ca2+ and sensitive to the Ca2+ channel antagonists, the tonic component more than the phasic component of response. Regardless of stimulant, K+ or methylfurmethide (MF), or component of response, the same rank order of antagonist activities is expressed, suggestive of a single structure–activity relationship and the existence of a single category of binding site which may, however, exist in several affinity states. High affinity binding of [3H]nitrendipine (KD = 1.1 × 10−10 M) occurs in bladder membranes, and similar high affinity binding was found in microsomal preparations from other smooth muscles including guinea pig and rat lung, rat vas deferens, uterus, and stomach. [3H]nitrendipine binding in the bladder was sensitive to displacement by other 1,4-dihydropyridines, paralleling their pharmacologic activities and showing excellent agreement with binding data previously obtained for guinea pig ileal smooth muscle. Comparison of pharmacologic data for inhibition of K+- and MF-induced responses by a common series of Ca2+ channel antagonists in bladder and ileum revealed excellent correlations. Neither pharmacologic nor binding studies suggest significant differences in Ca2+ channel antagonist properties in smooth muscle from bladder and intestine.

scholarly journals Isolation, Structural Characterization, and Bioactivity of a Novel Neuromedin U Analog from the Defensive Skin Secretion of the Australasian Tree Frog,Litoria caerulea

2000 ◽  
Vol 275 (7) ◽  
pp. 4549-4554 ◽  
Author(s):  
Amanda L. Salmon ◽  
Anders H. Johnsen ◽  
Michael Bienert ◽  
Gordon McMurray ◽  
Kiran A. Nandha ◽  
...  
Keyword(s):  
Structural Characterization ◽  
Tree Frog ◽  
Skin Secretion ◽  
Litoria Caerulea

scholarly journals AcT-2: A Novel Myotropic and Antimicrobial Type 2 Tryptophyllin from the Skin Secretion of the Central American Red-Eyed Leaf Frog,Agalychnis callidryas

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lilin Ge ◽  
Peng Lyu ◽  
Mei Zhou ◽  
Huiling Zhang ◽  
Yuantai Wan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Biological Activities ◽  
Antimicrobial Activities ◽  
Skin Secretion ◽  
Bladder Smooth Muscle ◽  
Amphibian Skin ◽  
Pharmacological Characterization ◽  
Rat Urinary Bladder ◽  
Agalychnis Callidryas

Tryptophyllins are a diverse family of amphibian peptides originally found in extracts of phyllomedusine frog skin by chemical means. Their biological activities remain obscure. Here we describe the isolation and preliminary pharmacological characterization of a novel type 2 tryptophyllin, named AcT-2, from the skin secretion of the red-eyed leaf frog,Agalychnis callidryas. The peptide was initially identified during smooth muscle pharmacological screening of skin secretion HPLC fractions and the unique primary structure—GMRPPWF-NH2—was established by both Edman degradation and electrospray MS/MS fragmentation sequencing. A. cDNA encoding the biosynthetic precursor of AcT-2 was successfully cloned from a skin secretion-derived cDNA library by means of RACE PCR and this contained an open-reading frame consisting of 62 amino acid residues with a single AcT-2 encoding sequence located towards the C-terminus. A synthetic replicate of AcT-2 was found to relax arterial smooth muscle (EC50= 5.1 nM) and to contract rat urinary bladder smooth muscle (EC50= 9.3 μM). The peptide could also inhibit the growth of the microorganisms,Staphylococcus aureus, (MIC = 256 mg/L)Escherichia coli(MIC = 512 mg/L), andCandida albicans(128 mg/L). AcT-2 is thus the first amphibian skin tryptophyllin found to possess both myotropic and antimicrobial activities.

scholarly journals THE ROLE OF CARBON MONOXIDE IN THE REGULATION OF ELECTRICAL AND CONTRACTILE PROPERTIES OF SMOOTH MUSCLE CELLS OF THE GUINEA PIG URETER

2014 ◽  
Vol 13 (1) ◽  
pp. 39-46
Author(s):  
I. V. Kovalyov ◽  
M. B. Baskakov ◽  
S. V. Gusakova ◽  
T. A. Idamzhapova ◽  
Yu. G. Birulina ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Smooth Muscles ◽  
Muscle Cells ◽  
Contractile Properties ◽  
Biologically Active

Carbon monoxide CO, as well as nitric oxide and hydrogen sulfide, make up the family of labile biological mediators termed gasotransmitters. We hypothesized that CO may be involved in the mechanisms of regulation electrical and contractile properties of smooth muscles.The effects of carbon monoxide donor CORM II (tricarbonyldichlororuthenium(II)-dimer) on the electrical and contractile activities of smooth muscles of the guinea pig ureter were studied by the method of the double sucrose bridge. This method allows to register simultaneously the parameters of the action potential (AP) and the contraction of smooth muscle cells (SMCs), caused by an electrical stimulus.CORM II in a concentration of 10 mmol has reduced the amplitude of contractions SMCs to (86.5 ± 9.7)% (n = 6, p < 0.05), the amplitude of the AP to (88.9 ± 4.2)% (n = 6, p < 0.05) and the duration of the plateau of the AP to (91.7 ± 6.0)% (n = 6, p < 0.05). On the background of the action of biologically active substances (phenylephrine, 10 µmol or histamine, 10 µmol), these effects of CORM II amplified. The inhibitory action of СORM II on the parameters of the contractile and electrical activities of the smooth muscles of guinea pig ureter has been decreased by blocking potassium channels in membrane of SMCs by tetraethylammonium chloride (TEA) оr inhibition of soluble guanylate cyclase (ODQ [1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-l-one]). On the background of TEA (5 mmol), a donor of CO (10 mmol) caused a reduction the amplitude of contraction SMCs to (87.0 ± 10.8)% (n = 6, p < 0.05), the amplitude of the AP to (91.7 ± 6.4)% (n = 6, p < 0.05) and the duration of the plateau of the AP to (93.4 ± 7.5)% (n = 6, p < 0.05). After the pretreatment of ODQ (1 µmol) adding CORM II (10 mmol) in solution has resulted to augment of the amplitude of contraction ureteral smooth muscle strips to (90.9 ± 4.2)% (n = 6, p < 0.05), the amplitude of the AP to (97.2 ± 10.3)% (n = 6, p < 0.05) and the duration of the plateau of the AP to and (99.7 ± 10.0)% (n = 6, p < 0.05).Thus, can be argued the inhibitory effect of carbon monoxide on the electrical and contractile activities of the guinea pig ureter SMCs is due to changes in the ionic conductivity of the membranes, above all with increasing the potassium conductance or activation of soluble guanylate cyclase.

PRELIMINARY STUDY OF ANTIMICROBIAL ACTIVITY OF THE SKIN SECRETIONS OF MALAYSIAN FROGS

2016 ◽  
Vol 78 (6-5) ◽  
Author(s):  
Zainon A. Rahman ◽  
Mohamad Faiz Foong Abdullah ◽  
Wan Mohamad Syahmin Wan Azmi ◽  
Aziyah Abdul-Aziz
Keyword(s):  
Antimicrobial Activity ◽  
Bioactive Compounds ◽  
Frog Skin ◽  
Antimicrobial Properties ◽  
Antimicrobial Effect ◽  
Skin Secretion ◽  
Gram Positive Bacteria ◽  
Microbial Infections ◽  
Skin Secretions ◽  
Preliminary Study

Bioactive compounds that exhibit antimicrobial properties in frogs are parts of the animal defense against microbial infections.  The lyophilized frog’s skin secretions containing varies bioactive compounds were subjected to screen for their antimicrobial activity. This study was conducted as part of an effort on the search of antimicrobial peptides (AMPs) profiles of Malaysian frogs. The results indicate the collected frog skin secretion has antimicrobial effect against Gram-negative and Gram-positive bacteria.  BLAST and standard phylogenetics were used to establish a preliminary identity of the frog samples.

scholarly journals Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Siti Junaidah Ahmad ◽  
Mohd Badrin Hanizam Abdul Rahim ◽  
Syarul Nataqain Baharum ◽  
Mohd Shukri Baba ◽  
Noraziah Mohamad Zin
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Bioactive Compounds ◽  
Antimalarial Activity ◽  
Classical Method ◽  
Biologically Active ◽  
Gram Positive Bacteria ◽  
H Nmr ◽  
Wide Range ◽  
Bioassay Guided Fractionation

Natural products continue to play an important role as a source of biologically active substances for the development of new drug.Streptomyces, Gram-positive bacteria which are widely distributed in nature, are one of the most popular sources of natural antibiotics. Recently, by using a bioassay-guided fractionation, an antimalarial compound, Gancidin-W, has been discovered from these bacteria. However, this classical method in identifying potentially novel bioactive compounds from the natural products requires considerable effort and is a time-consuming process. Metabolomics is an emerging “omics” technology in systems biology study which integrated in process of discovering drug from natural products. Metabolomics approach in finding novel therapeutics agent for malaria offers dereplication step in screening phase to shorten the process. The highly sensitive instruments, such as Liquid Chromatography-Mass Spectrophotometry (LC-MS), Gas Chromatography-Mass Spectrophotometry (GC-MS), and Nuclear Magnetic Resonance (1H-NMR) spectroscopy, provide a wide range of information in the identification of potentially bioactive compounds. The current paper reviews concepts of metabolomics and its application in drug discovery of malaria treatment as well as assessing the antimalarial activity from natural products. Metabolomics approach in malaria drug discovery is still new and needs to be initiated, especially for drug research in Malaysia.

Expression of myosin isoforms in smooth muscle cells in the corpus cavernosum penis

1998 ◽  
Vol 275 (4) ◽  
pp. C976-C987 ◽  
Author(s):  
Michael E. DiSanto ◽  
Ze Wang ◽  
Chandrakala Menon ◽  
Yongmu Zheng ◽  
Thomas Chacko ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Amino Acid ◽  
Smooth Muscles ◽  
Corpus Cavernosum ◽  
Muscle Cells ◽  
Myosin Isoforms ◽  
Bladder Smooth Muscle ◽  
Rt Pcr ◽  
Two Dimensional Gel Electrophoresis ◽  
Resting Tone

Corpus cavernosum smooth muscle (CCSM) in the penis is unique in that it exhibits a high resting tone and, on stimulation, the muscle cells relax, allowing cavernous spaces to fill with blood, which results in an erection (tumescence). During detumescence, the muscle cells contract and return to the state of high resting tone. This study was undertaken to determine whether CCSM with these unique properties contains myosin isoforms typical of aorta or bladder smooth muscles, muscles that exhibit tonic and phasic characteristics, respectively. RT-PCR revealed that normal CCSM contains an SM2/SM1 mRNA ratio of 1.2:1 (similar to the rabbit aorta). Approximately 31% of the myosin heavy chain transcripts possess a 21-nt insert (predominant in bladder smooth muscle but not expressed in aorta) that encodes the seven-amino acid insert near the NH2-terminal ATP binding region in the head portion of the myosin molecule found in SMB, with the remaining mRNA being noninserted (SMA). Quantitative competitive RT-PCR revealed that the CCSM possesses ∼4.5-fold less SMB than the bladder smooth muscle. Western blot analysis using an antibody specific for the seven-amino acid insert reveals that both SM1 and SM2 in the CCSM contain the seven-amino acid insert. Furthermore, SMB containing the seven-amino acid insert was localized in the CCSM by immunofluorescence microscopy using this highly specific antibody. The analysis of the expression of LC17isoforms a and b in the CCSM revealed that it is similar to that of bladder smooth muscle. Thus the CCSM possesses an overall myosin isoform composition intermediate between aorta and bladder smooth muscles, which generally express tonic- and phasiclike characteristics, respectively. Two-dimensional gel electrophoresis showed a relatively low level (∼10%) of Ca2+-dependent light-chain (LC20) phosphorylation at the basal tone, which reaches ∼23% in response to maximal stimulation. The presence of noninserted and inserted myosin isoforms with low and high levels of actin-activated ATPase activities, respectively, in the CCSM may contribute to the ability of the CCSM to remain in a state of high resting tone and to relax rapidly for normal penile function.

scholarly journals Balteatide: A Novel Antimicrobial Decapeptide from the Skin Secretion of the Purple-Sided Leaf Frog,Phyllomedusa baltea

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Lilin Ge ◽  
Xiaole Chen ◽  
Chengbang Ma ◽  
Mei Zhou ◽  
Xinping Xi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Rational Design ◽  
Frog Skin ◽  
Biologically Active ◽  
Single Amino Acid ◽  
Haemolytic Activity ◽  
Amino Acid Difference ◽  
Amino Acid Residues ◽  
Skin Secretion ◽  
Skin Secretions

The skin secretions of Neotropical phyllomedusine leaf frogs have proven to be a rich source of biologically active peptides, including antimicrobials. The major families of antimicrobial peptides (AMPs) reported are the dermaseptins and phylloseptins and the minor families are the dermatoxins, phylloxins, plasticins, distinctins, and medusins. Here, we report a novel AMP of 10 amino acid residues (LRPAILVRIKamide), named balteatide, from the skin secretion of wild Peruvian purple-sided leaf frogs,Phyllomedusa baltea. Balteatide was found to exhibit a 90% sequence identity with sauvatide, a potent myotropic peptide from the skin secretion ofPhyllomedusa sauvagei. However, despite both peptides exhibiting only a single amino acid difference (I/T at position 9), sauvatide is devoid of antimicrobial activity and balteatide is devoid of myotropic activity. Balteatide was found to have differential activity against the Gram-positive bacterium,Staphylococcus aureus; the Gram-negative bacterium,Escherichia coli; and the yeast,Candida albicans, and unusual for phyllomedusine frog skin AMPs, was most potent (MIC 32 mg/L) against the yeast. Balteatide was also devoid of haemolytic activity up to concentrations of 512 mg/L. Phyllomedusine frog skin secretions thus continue to provide novel AMPs, some of which may provide templates for the rational design of new classes of anti-infective therapeutics.

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