SOMATOSTATIN 2A RECEPTOR IS EXPRESSED BY ENTERIC NEURONS, AND BY INTERSTITIAL-CELLS OF CAJAL AND ENTEROCHROMAFFIN-LIKE CELLS OF THE GASTROINTESTINAL-TRACT

Somatostatin exerts multiple effects by activating distinct G protein- coupled receptors. Here we report the cellular sites of expression of the somatostatin subtype 2A (sst(2A)) receptor in the rat enteric nerv ous system by using a C-terminus-specific, affinity-purified antiserum and immunohistochemistry. Antibody specificity was confirmed by the c ell surface staining of human embryonic kidney 293 cells expressing th e sst(2A) receptor, the lack of staining of cells expressing the somat ostatin subtype 2B receptor, and the abolition of staining by preincub ating the antiserum with the C-terminus peptide used for immunization, sst(2A(361-369)). The sst(2A) receptor antibody recognized a broad 80 kDa band on Western blots of membranes prepared from cells transfecte d with sst(2A) receptor cDNA; following receptor membrane deglycosylat ion, the antibody detected an additional 40 kDa band. In the enteric n ervous system, the sst(2A) antibody primarily stained neurons of the m yenteric and submucosal plexuses, and abundant fibers distributed to t he muscle, mucosa, and vasculature. Immunoreactive staining was also o bserved in non-neuronal cells, including presumed interstitial cells o f Cajal of the intestine and enterochromaffin-like cells of the stomac h. Fibers expressing sst(2A) receptor immunoreactivity were often in c lose proximity to D cells of the gastric and intestinal mucosa. Coloca lization of somatostatin and sst(2A) receptor immunoreactivities was n ot observed in endocrine cells nor in enteric neurons. Double-label im munohistochemistry revealed colocalization of sst(2A) and vasoactive i ntestinal peptide immunoreactivities in enteric neurons. The multiple types of cells expressing the sst(2A) receptor, including enteric neur ons and nonneuronal structures, in addition to the relationship betwee n somatostatin and sst(2A) receptor elements, provide evidence that th e sst(2A) receptor mediates somatostatin effects in the gastrointestin al tract via neuronal and paracrine pathways. (C) 1997 Wiley-Liss, Inc .