Two collaborative studies were performed during the year in this project. Somatostatin and its synthetic analogues used clinically commonly have effects on gastrointestinal motility including the colonic muscle. Both studies were aimed at defining the ability of the neuropeptide somatostatin to alter colonic motility. To address this issue the effect of somatostatin (SS) on human colonic muscle cells was examined as well as the classes of somatostatin receptors (sst) on guinea pig colonic smooth muscle cells defined. In the study of human colonic tissue enzymatic digestion of surgical specimens from human colon were prepared and somatostatin-14 (SS-14), somatostatin-28 (SS-28), as well as the synthetic somatostatin analogue, octreotide stimulated a slight, but significant contraction as well as inhibited contraction caused by other more efficacious stimulants. These studies demonstrate somatostatin receptors (sst) are present on human circular muscle, likely of subtype 2,3, or 5 because octreotide only has a high affinity for these 3 sst subtypes. There are 5 subtypes of somatostatin receptor (sst-1-5). To define the subtypes further in colonic muscle, partial sequences of the guinea pig sst-1-5 were cloned and found to have 80-99% homology to the human sst-1-5. In isolated colonic smooth muscle cells as well as cultured smooth muscle cells, sst-1-5 were all found by PCR. The sst mRNA levels were too low to be detected on Northern blots. In previous studies on isolated guinea pig colonic smooth muscle cells octreotide was found to have contractile effects identical to SS-14 or SS-28 suggesting the sst subtypes 2,3, or 5 were mediating the contractile effects. Because sst1 and sst4 were also found on these cells by PCR our results suggest these sst subtypes have a noncontractile function in colonic smooth muscle cells.
