scholarly journals Deciphering the function of the CNGB1b subunit in olfactory CNG channels

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Vasilica Nache ◽  
Nisa Wongsamitkul ◽  
Jana Kusch ◽  
Thomas Zimmer ◽  
Frank Schwede ◽  
...  

Abstract Olfactory cyclic nucleotide-gated (CNG) ion channels are key players in the signal transduction cascade of olfactory sensory neurons. The second messengers cAMP and cGMP directly activate these channels, generating a depolarizing receptor potential. Olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b. So far the exact role of the modulatory subunits for channel activation is not fully understood. By measuring ligand binding and channel activation simultaneously, we show that in functional heterotetrameric channels not only the CNGA2 subunits and the CNGA4 subunit but also the CNGB1b subunit binds cyclic nucleotides and, moreover, also alone translates this signal to open the pore. In addition, we show that the CNGB1b subunit is the most sensitive subunit in a heterotetrameric channel to cyclic nucleotides and that it accelerates deactivation to a similar extent as does the CNGA4 subunit. In conclusion, the CNGB1b subunit participates in ligand-gated activation of olfactory CNG channels and, particularly, contributes to rapid termination of odorant signal in an olfactory sensory neuron.

2003 ◽  
Vol 1 (1) ◽  
pp. 25-32 ◽  
Author(s):  
G. Spoto ◽  
A. Contento ◽  
M. Di Nicola ◽  
G. Bianchi ◽  
C. Di Giulio ◽  
...  

Phosphodiesterase activity was tested on homogenized eyes of young and old rats kept in hypoxic and hyperoxic conditions, with the aim of correlating any difference in PDE activity with aging and variations in atmospheric oxygen contents. The activities of the two enzymes, cAMP phosphodiesterase (cAMP-PDE) and cGMP phosphodiesterase (cGMP-PDE), were tested. Phosphodiesterases seem to be particularly susceptible to variations in oxygen tension, suggesting an important role of cyclic nucleotides in cellular adaptive processes. Particularly, cAMP-PDE activity increases lightly both in hypoxic and hyperoxic conditions in young and old rats. For cGMP-PDE activity of young rats, a similar behaviour to cAMP-PDE activity is observed with a similar increase in hypoxic and hyperoxic conditions respect to the control rats. Instead old rats seem to be quite insensible to hypoxia, while they show a fair increase in cGMP-PDE activity in the case of hyperoxia. The second messengers cAMP and cGMP play important roles in mediating the biological effects of a wide variety of first messengers. The intracellular levels of cyclic nucleotides depend upon rates of synthesis and degradation, actuated, respectively, by cyclases and phosphodiesterases (PDEs). Therefore, PDEs seem to play an important role in a wide variety of physiological processes.


1985 ◽  
Vol 248 (5) ◽  
pp. H745-H749 ◽  
Author(s):  
G. Bkaily ◽  
N. Sperelakis

The role of guanosine 5'-cyclic monophosphate (cGMP) in the regulation of the ionic slow channels in heart muscle is less well known than that of adenosine 3,'5'-cyclic monophosphate (cAMP). The effects of intracellular injection of cAMP and cGMP in cultured chick embryonic heart (ventricular) cells by the liposome method were studied. Injection of cAMP into the cells induced spontaneous slow action potentials that could be blocked by verapamil and nifedipine. Injection of cGMP blocked on-going slow action potentials, and this effect was reversed by increasing cAMP. Thus both cAMP and cGMP are involved in the regulation of the slow calcium channels in myocardial cells, and the two cyclic nucleotides are antagonistic.


1991 ◽  
Vol 260 (5) ◽  
pp. G764-G769 ◽  
Author(s):  
S. Rattan ◽  
C. Moummi ◽  
S. Chakder

This investigation examined and compared the role of cyclic nucleotides in the mediation of internal anal sphincter (IAS) relaxation caused by the addition of neuropeptide calcitonin gene-related peptide (CGRP) and atrial natriuretic factor (ANF). The studies were performed in vitro on smooth muscle strips of opossum IAS. The relaxation produced by CGRP and ANF was examined before and after the addition of tetrodotoxin (TTX) (1 x 10(-6)M). At this concentration, TTX did not have any significant effect on the relaxation produced by either CGRP or ANF, suggesting that these peptides act directly on the smooth muscle. Addition of CGRP (3 x 10(-6) M) produced the maximal relaxation and significantly increased cAMP content without changing cGMP. On the other hand, addition of ANF (3 x 10(-6) M) caused a similar fall in IAS tension that was accompanied by a significant elevation in cGMP without any change in cAMP content. The rises in the levels of cyclic nucleotides preceded the onset of fall in the resting tension of IAS. Our results demonstrate that CGRP and ANF relax isolated strips of opossum IAS by their action directly at the smooth muscle and that this relaxation is associated with an increase in cAMP and cGMP, respectively. The studies suggest the presence of both cAMP and cGMP pathways in the IAS and that the relaxation of IAS smooth muscle in response to different peptides may occur via a specific intracellular biochemical pathway.


2004 ◽  
Vol 5 (1) ◽  
pp. 17-38 ◽  
Author(s):  
Avinash R. Shenoy ◽  
K. Sivakumar ◽  
A. Krupa ◽  
N. Srinivasan ◽  
Sandhya S. Visweswariah

Cyclic nucleotides are well-known second messengers involved in the regulation of important metabolic pathways or virulence factors. There are six different classes of nucleotide cyclases that can accomplish the task of generating cAMP, and four of these are restricted to the prokaryotes. The role of cAMP has been implicated in the virulence and regulation of secondary metabolites in the phylum Actinobacteria, which contains important pathogens, such asMycobacterium tuberculosis, M. leprae, M. bovisandCorynebacterium, and industrial organisms from the genusStreptomyces. We have analysed the actinobacterial genome sequences found in current databases for the presence of different classes of nucleotide cyclases, and find that only class III cyclases are present in these organisms. Importantly, prominent members such asM. tuberculosisandM. lepraehave 17 and 4 class III cyclases, respectively, encoded in their genomes, some of which display interesting domain fusions seen for the first time. In addition, a pseudogene corresponding to a cyclase fromM. aviumhas been identified as the only cyclase pseudogene inM. tuberculosisandM. bovis. TheCorynebacteriumandStreptomycesgenomes encode only a single adenylyl cyclase each, both of which have corresponding orthologues inM. tuberculosis. A clustering of the cyclase domains in Actinobacteria reveals the presence of typical eukaryote-like, fungi-like and other bacteria-like class III cyclase sequences within this phylum, suggesting that these proteins may have significant roles to play in this important group of organisms.


1992 ◽  
Vol 262 (1) ◽  
pp. C91-C97 ◽  
Author(s):  
W. T. Wong ◽  
H. S. Nick ◽  
S. C. Frost

The differentiation of 3T3-L1 fibroblasts to adipocytes can be accelerated by the addition of 1-methyl-3-isobutylxanthine (MIX), insulin, and dexamethasone to the culture medium. During differentiation, we have demonstrated that the level of both annexin I mRNA and protein decreases. The half-times for this reduction were 2 h and 10 h for annexin I mRNA and protein, respectively. Of the added agents in the differentiation medium, only MIX caused a decline in annexin I expression in 3T3-L1 fibroblasts. The MIX effect in fibroblasts was reversible and required de novo transcription but not protein synthesis. Although MIX could be replaced by high levels of theophylline, neither agonists of the beta-adrenergic receptor nor intracellular second messengers, cAMP and cGMP, were able to reduce annexin I. The potential role of annexin I in cellular differentiation is discussed.


Author(s):  
Neha Mahajan ◽  
Pragyanshu Khare ◽  
Kanthi Kondepudi ◽  
Mahendra Bishnoi

Transient receptor potential ankyrin 1 (TRPA1) channel is a calcium permeable, non-selective cation channel, expressed in the sensory neurons and non-neuronal cells of different tissues. Initially studied for its role in pain and inflammation, TRPA1 has now functionally involved in multiple other physiological functions. TRPA1 channel has been extensively studied for modulation by pungent compounds present in the spices and herbs. In the last decade, the role of TRPA1 agonism in body weight reduction, secretion of hunger and satiety hormones, insulin secretion and thermogenesis, has unveiled the potential of the TRPA1 channel to be used as a preventive target to tackle obesity and associated comorbidities including insulin resistance in type 2 diabetes. In this review, we summarized the recent findings of TRPA1 based dietary/non-dietary modulation for its role in obesity prevention and therapeutics.


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