Localization Of Neurokinin-1 Receptor Research Articles

Elevated Neurokinin-1 Receptor Expression in Uterine Products of Conception Is Associated With First Trimester Miscarriages

BackgroundMiscarriage is a common complication of early pregnancy, mostly occurring in the first trimester. However, the etiological factors and prognostic and diagnostic biomarkers are not well known. Neurokinin-1 receptor (NK-1R) is a receptor of tachykinin peptide substance P (SP) and has a role in various pathological conditions, cancers, but its association with miscarriages and significance as a clinicopathological parameter are not studied. Accordingly, the present study aimed to clarify the localization and expression for NK-1R in human retained products of conception (POC). The role of NK-1R is not known in miscarriages.Materials and MethodsNK-1R expression was assessed in POC and normal placental tissues by immunohistochemistry. Three- to four-micrometer-thin sections of formalin-fixed paraffin-embedded tissues were used for this purpose. Tissues were processed and then immunohistochemically stained with NK-1R antibody. Brain tissue was used as control for antibody. Protein expression was evaluated using the nuclear labeling index (%). Tissues were counterstained with 3,3′-diaminobenzidine (DAB), and microscopy was performed at 10×, 20×, and 40× magnifications.ResultsTen human POC tissues and 10 normal placental tissues were studied by immunohistochemistry to demonstrate the localization of NK-1R. The expression of NK-1R protein was high in all the cases of both groups. NK-1R expression showed no notable differences among different cases of miscarriages as well as normal deliveries at full term regardless of the mother’s age and gestational age at which the event occurred. Statistically, no difference was found in both groups, which is in agreement with our hypothesis and previous findings.ConclusionThe expression of NK-1R was similar in all the cases, and it was intense. It shows that dysregulation of NK-1R along with its ligand SP might be involved in miscarriages and also involved in normal delivery. Our results provide fundamental data regarding this anti-NK-1R strategy. Thus, the present study recommends that SP/NK-1R system might, therefore, be considered as an emerging and promising diagnostic and therapeutic strategy against miscarriages. Hence, we report for the first time the expression and localization of NK-1R in POC. We suggest NK-1R antagonist in addition to the immunoglobulins and human chorionic gonadotropin to diagnose and treat spontaneous miscarriages.

Substance P Receptor in the Rat Heart and Regulation of Its Expression in Long-Term Diabetes.

Substance P (SP) is a neuropeptide engaged in the signal transmission of neural C fibers afferents in the myocardium. The actions of SP in the heart are extensive and they are mediated by the neurokinin 1 receptor (NK1R), a member of the tachykinin subfamily of G-protein coupled receptors. The receptors have been found in the heart, but to our knowledge, their exact localization in the heart has not been described yet. Here, we investigated the presence of NK1R protein in separate rat heart compartments by means of western blot and its tissue distribution by means of immunofluorescence. Specificity of NK1R immunolabeling was controlled by preabsorption of the antiserum with its corresponding peptide. Additionally, we investigated abundance of gene for NK1R in separated heart chambers by means of quantitative real-time PCR (RT-PCR). Relative abundance of NK1R mRNA was expressed as a ratio of target gene Cq value to Cq value of control gene – beta-actin. Finally, we studied abundance of NK1R mRNA in different cell types of heart isolated by laser capture microdissection. Immunofluorescence showed NK1R immunoreactivity on the surface of some intracardiac neurons and smooth muscle cells of coronary vessels. The results of quantitative RT-PCR indicate abundance of mRNA for NK1R in all heart chambers with highest level in the left atrium. The presence of NK1R mRNA was detected in some samples of dissected intracardiac neurons, but not in cardiomyocytes or smooth muscle cells of coronary vessels. In the course of long-term diabetes, a significant downregulation of the NK1R mRNA was seen in the right atrium and upregulation in the right ventricle 53 weeks after the induction of diabetes. Our results indicate localization of NK1R in some intracardiac neurons and smooth muscle cells. Impaired transcription of the NK1R gene in the diabetic heart may be induced by unidentified genes or factors involved in the development of diabetic cardiomyopathy.

An immunohistochemical localization of neurokinin-1 receptor in the adenomere of submandibular gland; Morphological relation to the substance P immunoreactive fibers

An immunohistochemical localization of neurokinin-1 receptor in the adenomere of submandibular gland; Morphological relation to the substance P immunoreactive fibers

Light- and electron-microscopic study of the distribution of axons containing substance P and the localization of neurokinin-1 receptor in bone.

Substance P (SP) is a neuropeptide that is released from axons of sensory neurons and causes signal transduction through the activation of the neurokinin-1 receptor (NK1-R). The present study demonstrates the distribution of SP-like-immunoreactive (SP-LI) axons and the localization of NK1-Rs in rat bone tissue using the avidin-biotin-peroxidase complex method. Axons with SP-LI were commonly found near the trabecular bone in the temporal bone marrow, but they were only sparsely distributed in the mandible, femur, and tibia. Immunoreactivity for NK1-Rs was found on the plasma membrane and in the cytoplasm of the osteoclasts. In the osteoblasts and osteocytes, a small number of weak, punctate immunoreactive products of NK1-Rs were distributed close to the plasma membrane. At the electron-microscopic level, immunoreactivity for NK1-R was distributed mainly in the whole cytoplasm, except for the clear zone of the osteoclasts, and in pit-like structures along the plasma membrane. The NK1-R-immunoreactive structures in the cytoplasm were divided into two types of organelles, consisting of vesicular and vacuolar structures (probably transport vesicles and early endosomes). In the osteoblasts and osteocytes, the number of NK1-R-positive vesicular structures was fewer than in the osteoclasts. These results thus suggest that SP secreted by the sensory axons could directly modulate bone metabolism via NK1-Rs.