Role of genetic variation in the cannabinoid type 1 receptor gene (CNR1) in the pathophysiology of human obesity

2010 ◽  
Vol 11 (5) ◽  
pp. 693-702 ◽  
Author(s):  
Dorit Schleinitz ◽  
Solveig Carmienke ◽  
Yvonne Böttcher ◽  
Anke Tönjes ◽  
Janin Berndt ◽  
...  
2006 ◽  
Vol 91 (4) ◽  
pp. 1513-1519 ◽  
Author(s):  
Annika Vaclavicek ◽  
Kari Hemminki ◽  
Claus R. Bartram ◽  
Kerstin Wagner ◽  
Barbara Wappenschmidt ◽  
...  

Context: The contribution of prolactin (PRL) through its receptor (PRLR) to the pathogenesis and progression of human mammary tumors has received recent attention. Objective: We investigated whether genetic variation in the PRL and PRLR genes is associated with the risk of breast cancer (BC). Design: We conducted a case-control study with a total of seven single nucleotide polymorphisms (SNPs). Setting: The study was conducted at an academic research laboratory and university clinics. Patients and Other Participants: A total of 441 German familial, unrelated BC cases and 552 controls matched by age, ethnicity, and geographical region participated in the study. Intervention(s): There were no interventions. Main Outcome Measures(s): SNP genotype and haplotype distributions and haplotype interactions were correlated with the risk of BC. Results: Two SNPs (rs1341239 and rs12210179) within the PRL promoter regions were significantly associated with increased risk in homozygotes for the variant alleles [odds ratio (OR), 1.67 and 95% confidence interval (CI), 1.11–2.50; and OR, 2.09 and 95% CI, 1.23–3.52, respectively]. The PRL haplotype containing the variant alleles of the promoter SNPs increased significantly the risk of BC (OR 1.42, 95%CI 1.07–1.90). A PRLR haplotype was associated with a significant decrease in BC risk (OR 0.69, 95% CI 0.54–0.89). An increasing number of PRL and PRLR risk haplotypes led to a significant trend of increasing risk for BC (χ2 = 12.15; P = 0.007). Conclusions: Genetic variation in the PRL and PRLR genes was shown to influence BC risk. Additional studies are needed to further clarify the role of the PRL and PRLR genes in the risk of BC.


2010 ◽  
Vol 67 (1) ◽  
pp. 78-80 ◽  
Author(s):  
Christina S. Barr ◽  
Scott A. Chen ◽  
Melanie L. Schwandt ◽  
Stephen G. Lindell ◽  
Hui Sun ◽  
...  

Author(s):  
Julie Desroches

This landmark paper by Agarwal and colleagues was published in 2007, when the exact contribution of the activation of the cannabinoid type 1 receptor (CB1) receptors expressed on the peripheral terminals of nociceptors in pain modulation was still uncertain. At that time, while it was clearly demonstrated that the central nervous system (CNS) was involved in the antinociceptive effects induced by the activation of the CB1 receptor, many strains of mice in which the gene encoding the CB1 receptor was deleted by conditional mutagenesis were used to study the specific role of these receptors in pain. Creating an ingenious model of genetically modified mice with a conditional deletion of the CB1 receptor gene exclusively in the peripheral nociceptors, Agarwal and colleagues were the first to unequivocally demonstrate the major role of this receptor in the control of pain at the peripheral level. In fact, these mutant mice lacking CB1 receptors only in sensory neurons (those expressing the sodium channel Nav1.8) have been designed to highlight that CB1 receptors on nociceptors, and not those within the CNS, constitute an important target for mediating local or systemic (but not intrathecal) cannabinoid analgesia. Overall, they have clarified the anatomical locus of cannabinoid-induced analgesia, highlighted the potential significance of peripheral CB1-mediated cannabinoid analgesia, and revealed important insights into how the peripheral endocannabinoid system works in controlling both inflammatory pain and neuropathic pain.


2021 ◽  
Vol 67 (1) ◽  
pp. 44-56
Author(s):  
M.A. Petrushenko ◽  
◽  
E.A. Petrushenko ◽  
E.A. Lukyanetz ◽  
◽  
...  

In mammals, the ankyrin ionotropic transient receptor potential type 1 (TRPA1) is the only member of the TRPA receptor gene subfamily. It is defined as a target for damaging and inflammatory effects in peripheral sensory neurons, which implies its functional role in the development of pain and neurogenic inflammation. Experimental studies indicate that calcium permeable non-selective ion receptor channel TRPA1 is activated by a number of exogenous irritant compounds, factors including low temperatures. This review describes the structure, properties, and physiological role of TRPA1 receptors.


2021 ◽  
pp. jeb.238816
Author(s):  
Luca Finetti ◽  
Marco Pezzi ◽  
Stefano Civolani ◽  
Girolamo Calò ◽  
Chiara Scapoli ◽  
...  

In insects, the tyramine receptor 1 (TAR1) has been shown to control several physiological functions, including olfaction. We investigated the molecular and functional profile of the Halyomorpha halys type 1 tyramine receptor gene (HhTAR1) and its role in olfactory functions of this pest. Molecular and pharmacological analyses confirmed that the HhTAR1 gene codes for a true TAR1. The RT-qPCR analysis revealed that HhTAR1 is expressed mostly in adult brain and antennae as well as in early development stages (eggs, 1st and 2nd instar nymphs). In particular, among the antennomeres that compose a typical H. halys antenna, HhTAR1 was more expressed in flagellomeres. Scanning electron microscopy (SEM) investigation revealed the type and distribution of sensilla on adult H. halys antennae: both flagellomeres appear rich in trichoid and grooved sensilla, known to be associated with olfactory functions. Through a RNAi approach, topically delivered HhTAR1 dsRNA induced a 50 % gene downregulation after 24 h in H. halys 2nd instar nymphs. An innovative behavioral assay revealed that HhTAR1 RNAi-silenced 2nd instar nymphs were less susceptible to the alarm pheromone component (E)-2 decenal as compared to control. These results provide critical information concerning the TAR1 role in olfaction regulation, especially alarm pheromone reception, in H. halys. Furthermore, considering the emerging role of TAR1 as target of biopesticides, this work opens the way for further investigation on innovative methods for controlling H. halys.


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