Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Therapeutic elastic tape reduces morbidity after wisdom teeth removal—a clinical trial

ObjectivesAlthough the extraction of an impacted third molar (3M) is a routine procedure, postoperative morbidities typically include swelling, pain, and trismus. The aim of the present study was to investigate whether the application of kinesiologic tape can improve the postoperative morbidities associated with 3M surgery, thereby improving the postoperative well-being of patients.Materials and methodsForty patients assigned for prospective 3M removal were randomized into two treatment groups (with/without kinesiologic tape). Facial swelling was quantified using a five-line measurement at six specific time points. Pain scores were assessed using a visual analog scale, and mouth opening range was assessed by means of standard calipers. In addition, all patients were asked to evaluate overall satisfaction and swelling (both groups) and the effect of the tape on movement and comfort (taped group only).ResultsThe postoperational application of kinesiologic tape reduced significantly all investigated parameters: swelling, pain, and trismus. Furthermore, patients with kinesiologic tape reported a significantly lower morbidity rate.ConclusionThe application of kinesiologic tape following a 3M surgery is a simple and economical, yet medically relevant approach.Clinical relevanceKinesiologic tape offers patients a less traumatic postoperational experience and therefore holds promise to enhance the quality of life of a large cohort of the population