0.3M of noradrenaline is administered the 2B adrenergic receptors there is a down regulation by 50%. The 2C adrenergic receptor endogenously expressed in the opposum kidney cell line also down regulates by approximately 50% after 0.3M of noradrenaline is administered. In contrast down regulation of the 2A adrenergic subtype stably transfected into the Chinese hamster ovary cell line reaches a 50% control only when 30M of noradrenaline (BYLUND et al 1997). This is a hundred fold greater than that required to down regulate the 2B or 2C subtypes. The significance of this observation is not fully understood, but it may represent a fundamental difference in the way in which receptors are regulated.From the this experiment it can be deduced that subtypes within the same receptor subfamily have different affinities to an endogenous agonist. When concentrations of this endogenous agonist are changed for example increased it can have profound effects pharmacologically and physiologically as observed in the PTSD study. Dysregulation can occur, and this is the centre of many illnesses particularly in the brain, for example Schizophrenia.Nausea and vomiting associated with chemotherapy and radiation in the cancer patient seriously reduces the quality of life, and may be so severe as to cause the patient to discontinue therapy. (MINER et al.1986) and (COSTALL et al. 1986) were first people to demonstrate that the 5-HT3 receptor antagonists can inhibit emesis. 5-HT3 antagonists block emesis by 5-HT3 antagonism at the central sites, i.e. in the nucleus tractus solitarius, area postrema and dorsal motor vagal nucleus, also in the periphery at 5-HT3 receptors on the afferent vagus nerve terminals. According to research chemotherapy and radiation affect serotoninergic function in the gut, causing a release of 5-HT from the enterochromaffin cells which stimulate 5-HT3 receptors on the v...
