Meningeal cells are targets and inactivation sites for the neuropeptide somatostatin

Transcripts of the somatostatin receptor subtypes sst(3) and sst(2) are expressed in meninges from rat brain as well as in immunocytochemical pure rat meningeal cells and rat fibroblasts in culture. mRNA of three other subtypes tested are absent or detected in trace amounts by reverse transcription-polymerase chain reaction. Presence of active receptors on the surface of meningeal cells and fibroblasts could be verified by direct visualisation of binding sites by affinity labelling with 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 agonist inhibited cell proliferation to about 80% of controls, after 24 h proliferation was stimulated to about 150% of controls. Apart from being targets for somatostatin, meningeal cells had a high capacity to inactivate the peptide by proteolytic degradation. By analysis of cleavage sites and use of specific inhibitors, endopeptidase-24.11 ('enkephalinase', neutral endopeptidase, neprilysin, EC 3.4.24.11) was identified to be responsible for the initial catabolism of the peptide whereas aminopeptidase(s) truncated the fragments. Thus, meningeal cells express transcripts of multiple somatostatin receptor subtypes and produce peptidases that inactivate the neuropeptide somatostatin.