In this study we examine the mechanism by which somatostatin (SRIF-14) inhibits cholecystokinin octapeptide- (CCK-8) but not substance P-mediated release of [3H]acetylcholine (ACh) from the guinea pig ileum. 2',5'-Dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of CCK-8 and forskolin but had no effect on substance-P-evoked release of [3H]ACh. Addition of theophylline enhanced the release of [3H]ACh stimulated by CCK-8 but not by substance P. These observations suggest that CCK-8, but not substance P, can stimulate cholinergic transmission via an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway. Somatostatin inhibited release of [3H]ACh evoked by CCK-8 and forskolin in a dose-related manner. CCK-8- and forskolin- but not substance P-evoked release of [3H]ACh were maximally inhibited in the presence of 10(-6) M somatostatin (49 +/- 5 and 48 +/- 7% of control, respectively). Pretreatment with pertussis toxin (inactivates inhibitory guanine nucleotide binding proteins) reversed the inhibitory effect of somatostatin on the release of [3H]ACh evoked by CCK-8. These observations suggest that CCK-8 but not substance P can stimulate [3H]ACh by a cAMP-dependent pathway. Somatostatin appears to inhibit the cAMP-dependent component of CCK-8-mediated cholinergic transmission via activation of a pertussis toxin-sensitive G protein.

No abstract

INTRODUCTION: DCL-101, a novel Pill Prep, is compositionally identical to standard 4L polyethylene glycol-electrolyte solution (PEG-ELS) and delivers the salt encapsulated, with PEG 3350 coadministered as a taste-free oral solution. The aim of this study was to compare the safety, taste, and tolerability of DCL-101 with 4L PEG-ELS in outpatients preparing for colonoscopy, with a secondary objective to assess efficacy. METHODS: This was a multicenter, randomized, investigator-blinded, phase 2 clinical trial of 45 adult patients undergoing outpatient colonoscopy. Patients were randomized 2:1 to either DCL-101 (3L in cohort 1; 4L in cohort 2) or 4L PEG-ELS, each administered with split dosing. Safety was assessed over 3 post-treatment clinic visits. Tolerability was measured using the Lawrance Bowel-Preparation Tolerability Questionnaire and the Mayo Clinic Bowel Prep Tolerability Questionnaire. Efficacy was determined by expert central readers, blinded to treatment, using the Ottawa Bowel Preparation Quality Scale, Boston Bowel Preparation Scale, and Aronchick scale. RESULTS: Both DCL-101 doses had superior taste and tolerability relative to 4L PEG-ELS. All adverse events were grade 1 with no significant differences in adverse events among the 3 regimens. There were no significant differences in efficacy among the 3 treatments as defined by the centrally read Ottawa Bowel Preparation Quality Scale, Boston Bowel Preparation Scale, or Aronchick scores. There were no inadequate preps as judged by the site endoscopist. DISCUSSION: DCL-101 Pill Prep is a novel strategy that vastly improves the taste and tolerability of PEG-ELS solutions with safety and efficacy comparable with split-dose 4L PEG-ELS solutions.

No abstract