EXPRESSION OF A BRAIN-TYPE CANNABINOID RECEPTOR (CB1) IN ALVEOLAR TYPE-II CELLS IN THE LUNG - REGULATION BY HYDROCORTISONE

Using the polymerase chain reaction with degenerate primers to identif y novel G-protein-coupled receptors of the rat alveolar Type II cell, we identified sequences expressed by the Type TI cell identical to the sequence of the rat brain cannabinoid receptor (CB1). The use of Nort hern blot analysis to examine expression of CB1 mRNA in rat tissues re vealed differences between the brain and lung. While rat brain express ed a 6.0 hb mRNA as previously described, rat lung expressed mRNA of 4 .5 and 6.0 kb. Isolated lung alveolar Type II cells also expressed mRN A of 4.5 and 6.0 kb as determined by Northern analysis. However, only freshly isolated Type II cells contained cannabinoid receptor mRNA. Re verse transcriptase-polymerase chain reaction (RT-PCR) failed to detec t CB1 mRNA in Type II cells maintained in culture for 1 or 2 days. We next determined developmental changes in lung CB1 mRNA expression usin g semi-quantitative RT-PCR. CB1 expression was detected as early as ge stational day 16 in rat lung and mRNA levels increased to fetal day 20 before birth, before declining to adult levels. Fetal rat lung explan ts were utilized to further examine the ontogeny and hormonal effects on CB1 mRNA expression. Hydrocortisone induced a dose-dependent expres sion in 15-day and 18-day explants, similar to previous results for su rfactant-associated proteins. Our results demonstrate expression of CB 1 mRNA in rat alveolar Type II cells and rat lung. This expression is ontogenically and hormonally regulated, with maximal expression noted just prior to birth in rat lung. Since CB1 mRNA is only expressed in f reshly isolated Type II cells, CB1 may be useful as a Type II cell mar ker.