Cardiac fibroblasts (CFs) are an important cellular component of myocardial responses to injury and to hypertrophic stimuli. We studied G protein-coupled receptors to understand how CFs integrate signals that activate G(q), G(s), and G(i). We predicted that the second messenger pathways present in CFs were distinct from those in cardiac myocytes and that unique signaling interactions existed in the CFs. ANG II, bradykinin, ATP, and UTP stimulated inositol phosphate (IP) production 2.2- to 7-fold. Each of these agonists elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) via release from the intracellular Ca(2+) storage compartment. Endothelin-1 (ET-1), carbachol, and norepinephrine failed to increase either IP production or [Ca(2+)](i). Although agonists that activated IP and Ca(2+) transients had no effect on cAMP production when administered alone, these agents potentiated the beta(2)-adrenergic response two- to fourfold. Hormones known to inhibit adenylyl cyclase activity in cardiac myocytes, such as ET-1 and carbachol, failed to lower the beta-adrenergic response in fibroblasts. Order of potency and inhibitor data indicate that the functional receptor subtypes in these cells are beta(2), P2Y(2), and AT(1) for isoproterenol, ATP, and ANG II, respectively. We conclude that CFs express functional G protein-linked receptors that couple to G(q) and G(s), with little or no coupling to G(i). The expression of receptors and their coupling to G(q)- but not to G(i)-linked responses distinguishes the signaling in CFs from that in myocytes. Furthermore, agonists that activate G(q) in CFs potentiate stimulation of G(s), an example of signaling cross talk not observed in adult myocytes. These data suggest that G protein-mediated signaling in CFs is unique and may contribute to the specificity of hormone and drug action on individual cell types within the heart.

Background and Goals To increase colorectal cancer screening among urban minorities, New York Presbyterian Hospital/Columbia University, with support from the New York City Department of Health and the Citywide Colon Cancer Control Coalition (C5), instituted a patient navigation and direct endoscopic referral system. We assessed the effect of this program on the volume of colonoscopy in this institution, which caters to a socioeconomically diverse patient population. Study We compared colonoscopy volume during the first year of the navigator program to the volume during the year prior to this program. We stratified on Medicaid status to assess the secular trend of screening rates. To assess quality during this period, we measured cecal intubation rates, preparation quality, and adenoma detection rates (ADR). Results Of the 749 patients assessed by patient navigators 678 (91%) underwent colonoscopy. Colonoscopy volume among Medicaid outpatients increased by 56% (957 to 1,489). Adenoma detection was 27% and the cecal intubation rate was 97%. Comparing navigated patients to non-navigated Medicaid outpatients, preparation quality was superior (34% versus 40% suboptimal, p=0.0282), though preparation quality remained inferior to that of private patients (20% suboptimal, p<0.0001). Conclusions Volume of colonoscopy increased, coinciding with the onset of the patient navigation program. This increase was nearly entirely due to a rise in colonoscopies among Medicaid outpatients, the principal focus of the navigator program. This increase in quantity was accomplished while maintaining an overall high level of quality as measured by cecal intubation rates and adenoma detection, although preparation quality requires further efforts at improvement.