MENINGEAL CELLS ARE TARGETS AND INACTIVATION SITES FOR THE NEUROPEPTIDE SOMATOSTATIN

Transcripts of the somatostatin receptor subtypes sst(3) and sst(2) ar e expressed in meninges from rat brain as well as in immunocytochemica l pure rat meningeal cells and rat fibroblasts in culture. mRNA of thr ee other subtypes tested are absent or detected in trace amounts by re verse transcription-polymerase chain reaction. Presence of active rece ptors on the surface of meningeal cells and fibroblasts could be verif ied by direct visualisation of binding sites by affinity labelling wit h a somatostatin gold conjugate. The metabolically stable somatostatin agonist SMS 201-995 (octreotide) had a time-dependent effect on the [ H-3]thymidine incorporation by meningeal cells: after 2-5 h, the agoni st inhibited cell proliferation to about 80% of controls, after 24 h p roliferation was stimulated to about 150% of controls. Apart from bein g targets for somatostatin, meningeal cells had a high capacity to ina ctivate the peptide by proteolytic degradation. By analysis of cleavag e sites and use of specific inhibitors, endopeptidase-24.11 ('enkephal inase', neutral endopeptidase, neprilysin, EC 3.4.24.11) was identifie d to be responsible for the initial catabolism of the peptide whereas aminopeptidase(s) truncated the fragments. Thus, meningeal cells expre ss transcripts of multiple somatostatin receptor subtypes and produce peptidases that inactivate the neuropeptide somatostatin.