We have completed the work on the localization of the cannabinoid type 2 receptor in the immune system and found that the receptors are present in B cells of the marginal zone in the spleen. This finding might explain the well known effects of marijuana on immune function and suggests the possible use of specific cannabinoid 2 antagonists to boost immunoglobulin production or the use of agonists to suppress immune function (in the cases of tissue transplantation for instance). A transgenic mouse that would lack the receptor for the cannabinoid 2 receptor has been successfully completed. Several constructs have been injected into stem cells and the mice (if they are viable) will be available in the near future. We have successfully mapped all somatostatin receptors in the pituitary gland and colocalized their mRNA with the different pituitary hormones. We also finished a study on the presence of receptors of the VIP family (VIP1, VIP2 and PACAP) in the rat testis and concluded that the well known effects of PACAP in the testis are due to its binding to the type 2 VIP receptor, and not the PACAP receptor - as previously thought. We are in the process of mapping and studying the distribution of somatostatin receptors in the peripheral tissues. Work has continued on the mechanisms involved in ulcer formation in the GI tract. We discovered that the parietal cells of the stomach are positive for tyrosine hydroxylase (TH) and dopamine. In collaboration with Graeme Eisenhoffer we found very high concentrations of dopamine in the gastric juice. With the help of Beth Hoffman and Bela Hunyady (NIMH, LCB) they have succeeded in isolating gastric mucosal cells, then measuring dopamine in these cells, and also quantitating TH activity in the superficial mucosal layer (GE). In situ hybridization histochemistry shows that the dopamine 1b (=D5) receptor is present in most epithelial and many lamina propria cells in the stomach and can be the target of this locally made dopamine. In this new non-neuronal dopamine system, dopamine might act as a hormone, since it is secreted into the stomach, and is stabile in an acidic environment.
| Hunyady, B; Palkovits, M; Mezey, E (2000) Vesicular monoamine transporters in the rat stomach. J Physiol Paris 94:123-30 |
| Mezey, E; Eisenhofer, G; Hansson, S et al. (1999) Non-neuronal dopamine in the gastrointestinal system. Clin Exp Pharmacol Physiol Suppl 26:S14-22 |
