Study of adenylate cyclase activity in NMS patients based on heterotype of α2B-AR gene

We want to clarify the effects of acute stress on patients with neuroleptic malignant syndrome (NMS). For this study, we investigated 12 subjects: 10 healthy and 2 patients with NMS. We primarily studied whether plasma adrenaline increases markedly at the onset of syncope. We started by investigating the disease’s epidemiology at the time of acute stress reaction. We analyzed the mechanism of molecular interaction and genetic polymorphisms of the α2B-AR gene. Particularly, we focused on the polymorphism sites in the position of Glu 301–303 in the glutamic acid 9 or 12 repeats number. Furthermore, we looked at the activity of adenylate cyclase (AC) which differs significantly among the three types: the heterotype of 9/12 and two homo genotypes of 12/12 and 9/9. Therefore, we investigated the adenylate cyclase activity of lymphocytes in blood at both normal times and times of stress during the head-up tilt test. Our results showed that the adenylate cyclase activity was higher in the heterotype than in the two homotypes in all three gene types when 10 μM adrenaline was administered into the plasma. In addition, two NMS patients showed significantly lower AC activity, (p<0.05, t-test) than 5 healthy heterotypical subjects based on plasma adrenaline at 10μM. Interestingly, NMS patients were found to have lower adenylate cyclase activity when administrated 10 μM of plasma adrenaline than healthy subjects at both head-up 70° tilt stress or at the base line. From these results, we hypothesized that the adenylate cyclase activity in NMS patients is low during times of stress.