Characterization of the role of calcium and sodium channels in the stimulus secretion coupling of 5-hydroxytryptamine release from porcine enterochromaffin cells.
Strips of the porcine small intestine were incubated in vitro and the outflow of 5-hydroxytryptamine (5-HT) was determined by HPLC with electrochemical detection. Spontaneous outflow of 5-HT from the porcine small intestine was reduced by about 70% after removal of the extracellular calcium or by addition of 1 mM gadolinium. Tetrodotoxin reduced the outflow of 5-HT by 30%, an effect which has previously been shown to be caused by inhibition of an excitatory cholinergic input. The sodium channel opener veratridine (up to 100 microM) did not affect the outflow of 5-HT. omega-Conotoxin GVIA (500 nM) or nifedipine (10 microM) reduced the outflow of 5-HT only by about 50%, and their effects were not additive. The inhibitory effects of omega-conotoxin GVIA occurred also in the presence of tetrodotoxin. Elevation of extracellular potassium to 40 mM caused a marked and sustained increase in 5-HT outflow. High potassium evoked release of 5-HT was blocked by omega-conotoxin GVIA, nifedipine and gadolinium. When omega-conotoxin GVIA and nifedipine were present in combination, their inhibitory effects on the high potassium evoked 5-HT release vanished. BAY K 8644 (1-10 microM) did not facilitate 5-HT release, but markedly reduced the spontaneous and high potassium evoked release of 5-HT. In conclusion, the enterochromaffin cells are endowed with multiple calcium channels, but voltage-sensitive calcium channels of a neuronal L-type which are sensitive to dihydropyridines and omega-conotoxin GVIA appear to play a major role.
Racké
K
K
Department of Pharmacology, J.W. Goethe-University Frankfurt, Federal Republic of Germany.
Schwörer
H
H
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004759:Enterochromaffin Cells / Q000378:metabolism*; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013552:Swine
D015220:Calcium Channels; D015222:Sodium Channels; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D011188:Potassium