Cannabinoid 1 receptors are expressed by nerve growth factor- and glial cell-derived neurotrophic factor-responsive primary sensory neurones

Expression of the cannabinoid 1 (CB1) receptor and its regulation were studied in the different nociceptive and non-nociceptive sub-populations of cultured primary sensory neurones of adult rats. Bandairaea simplicifolia isolectin B4 (IB4) binding and calcitonin gene-related peptide (CGRP) immunostaining were used to distinguish between the glial cell-derived neurotrophic factor (GDNF)- and nerve growth factor (NGF)-responsive nociceptive and the non-nociceptive primary sensory neurones while a specific CB1 receptor antibody was used to study the expression of the CB1 receptor protein. About half of the total number of primary sensory neurones (47 +/- 3.2%) cultured for 1 day in the presence of both neurotrophic factors (50 ng/ml each) showed CB1 receptor-like immunostaining, whereas 21.8 +/- 3.3% and 32.7 +/- 5.6% of the neurones showed CGRP-like immunopositivity and IB4 binding, respectively. A proportion of the CB1 receptor-like immunopositive neurones was immunostained for CGRP (31.7 +/- 5%) and IB4 (48.2% +/- 7.5), with a minimal (1%) co-expression of CGRP and IB4 binding. About a fifth of the CB1 receptor-like immunopositive neurones did not show either CGRP-like immunostaining or IB4 binding. To find out whether CB I receptor expression in nociceptive primary sensory neurones is regulated by GDNF or NGF, cultures were grown in the presence or absence of the neurotrophic factors for 7 days. Vanilloid receptor 1 (VR1) immunostaining was used as a control marker to monitor the effect of the neurotrophins. In cultures maintained in the presence of both factors (50 ng/ml each) 51 +/- 2.6% and 42.4 +/- 1.2% of the cells showed CB1 receptor-like and VR1-like immunostaining, respectively, In cultures grown for 7 days in the absence of either of the neurotrophic factors the relative number of VR1-like immunopositive cells decreased to 13.4 +/- 2.7%, whereas the relative number of CB1 receptor-like immunopositive neurones was unchanged (50.6 +/- 1.1%). Our data suggest that the CB1 receptor is expressed in all of the three major sub-populations of primary sensory neurones and that the CB1 receptor expression is not regulated by either NGF or GDNF. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.