Effects of imidazoline compounds on cytoplasmic Ca2+ concentration and ATP-sensitive K+ channels in pancreatic B-cells.
Phentolamine, an alpha-adrenoceptor-blocking agent with an imidazoline structure, induces an increase in the cytoplasmic Ca2+ concentration of pancreatic B-cells. This effect occurs at a concentration (32 microM) at which phentolamine is able to enhance glucose-induced insulin secretion. The increase in cytoplasmic Ca2+ concentration caused by phentolamine is additive to the one elicited by a maximally effective concentration of tolbutamide (100 microM). Imidazoline-binding sites in insulin-secreting HIT cells can also be occupied by the guanidinium compound guanabenz, which was found to be a potent and reversible blocker of ATP-dependent K(+)-channels in B-cells. In contrast to phentolamine, guanabenz blocks the ATP-dependent K(+)-channels only in the inside-out mode, but not in the cell-attached mode of the patch-clamp technique. In conclusion, imidazolines and structurally related compounds block ATP-dependent K(+)-channels by binding to the cytoplasmic face of the plasma membrane, and may have effects on other ion channels which contribute to the elevation of cytoplasmic Ca2+ concentration and, consequently, to insulin release.
Rustenbeck
I
I
Institute of Pharmacology, University of Göttingen, Germany.
Kowalewski
R
R
Herrmann
C
C
Dickel
C
C
Ratzka
P
P
Hasselblatt
A
A
D000255:Adenosine Triphosphate / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D005470:Fluorometry; D006143:Guanabenz / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018408:Patch-Clamp Techniques; D010646:Phentolamine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D014044:Tolbutamide / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007004:Hypoglycemic Agents; D007093:Imidazoles; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D006143:Guanabenz; D002118:Calcium; D010646:Phentolamine