Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl− channels important for anion secretion, we herein performed experiments on Capan-1, a human pancreatic duct cell line, using open-circuit Ussing chamber and gramicidin-perforated patch-clamp techniques. The luminal addition of adenosine increased the negative transepithelial potential difference (V te) in Capan-1 monolayers with a half-maximal effective concentration value of approximately 10 μM, which corresponded to the value obtained on whole-cell Cl− currents in Capan-1 single cells. The effects of adenosine on V te, an equivalent short-circuit current (I sc), and whole-cell Cl− currents were inhibited by CFTRinh-172, a cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel inhibitor. The adenosine A2B receptor agonist, BAY 60-6583, increased I sc and whole-cell Cl− currents through CFTR Cl− channels, whereas the A2A receptor agonist, CGS 21680, had negligible effects. The A2B receptor antagonist, PSB 603, inhibited the response of I sc to adenosine. Immunohistochemical analysis showed that the A2A and A2B receptors colocalized with Ezrin in the luminal membranes of Capan-1 monolayers and in rat pancreatic ducts. Adenosine elicited the whole-cell Cl− currents in guinea pig duct cells. These results demonstrate that luminal adenosine regulates anion secretion by activating CFTR Cl− channels via adenosine A2B receptors on the luminal membranes of Capan-1 cells. The present study endorses that purinergic signaling is important in the regulation of pancreatic secretion.
To examine the patterns of drug prescription for the treatment of attention-deficit/hyperactivity disorders in Japanese children and adolescents. We conducted a cross-sectional survey on December 1, 2013, on patients aged 19 or less in two national mental hospitals. Patients who were prescribed at least one drug for the treatment of attention-deficit/hyperactivity disorders (anti-ADHD drug) were analyzed. Data were extracted on gender, age, and types and doses of psychotropic drugs. Data on the patients’ diagnoses were not collected. The patients included 87 males and 26 females, with a mean age (standard deviation) of 12.4 (2.8) years. Of these 113 patients, 70 (61.9%) patients received the psychostimulant OROS methylphenidate (OROS-MPH) only, 26 (23.0%) received atomoxetine (ATMX), a selective noradrenalin reuptake inhibitor only, and 17 (15.0%) received the combination OROS-MPH/ATMX therapy. Antipsychotics were concurrently prescribed in 51 (45.1%) patients. Mood stabilizers were co-prescribed in 31 (27.4%) cases. Antidepressants were co-prescribed in 8 (7.1%) patients. Anxiolytics/hypnotics were concurrently prescribed in 23 (20.4%) patients. Nearly one-sixth of patients, aged 19 or less and treated with anti-ADHD drug therapy in Japanese mental hospitals, were prescribed OROS-MPH/ATMX combination therapy. In addition, almost half of these young patients on anti-ADHD drugs were co-prescribed antipsychotics.
