beta-Adrenergic regulation of ion transport in pancreatic ducts: patch-clamp study of isolated rat pancreatic ducts.
OBJECTIVE
In the intact pancreas, bicarbonate secretion is thought to be controlled by a number of regulators, including adrenergic agonists. The aim of this study was to investigate the effects of adrenergic agonists on pancreatic ducts, which are the site of bicarbonate secretion.


METHODS
Small intralobular ducts were isolated from rat pancreas and studied in vitro by the whole-cell patch clamp technique. Cell membrane voltages and currents were indicators of cellular ion transport. In some ducts, intracellular Ca2+ activity was measured by fluorescence optical methods.


RESULTS
Unstimulated duct cells had a membrane voltage (Vm) of about -50 mV. Isoproterenol had a concentration-dependent effect on Vm; at 10(-7) mol/L, it depolarized Vm by 20-25 mV and the cell conductance increased by 100 nanosiemens. These effects were a result of opening of luminal Cl- channels. Phenylephrine had much smaller effects. At comparable concentrations, it depolarized Vm by a few millivolts. Neither agonist had significant effects on intracellular Ca2+.


CONCLUSIONS
This study provides the first direct evidence that adrenergic stimulation, namely, that of beta-adrenoceptors, controls ion transport in pancreatic ducts. Similar to secretin, isoproterenol stimulation leads to opening of luminal Cl- channels, and HCO3- enters the lumen in exchange for Cl-.
Novak
I
I
August Krogh Institute, University of Copenhagen, Copenhagen, Denmark. inovak@aki.ku.dk
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004553:Electric Conductivity; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D010183:Pancreatic Ducts / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013997:Time Factors; D014544:Uridine Triphosphate / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D000255:Adenosine Triphosphate; D002217:Carbachol; D007545:Isoproterenol; D002118:Calcium; D014544:Uridine Triphosphate; D004837:Epinephrine; D010646:Phentolamine