| Autor: |
BODDEKE, HWGM, HOFFMAN, BJ, PALACIOS, JM, KNOT, H, HOYER, D |
| Přispěvatelé: |
Translational Immunology Groningen (TRIGR) |
| Jazyk: |
angličtina |
| Rok vydání: |
1993 |
| Předmět: |
|
| Zdroj: |
Naunyn-Schmiedebergs Archives of Pharmacology, 347(2), 119-124. SPRINGER |
| ISSN: |
0028-1298 |
| Popis: |
Functional responses to stimulation of rat 5-HT1C receptors expressed in A9 cells were studied using whole cell voltage clamp and calcium recording techniques. Stimulation of 5-HT1C receptors evoked outward currents clamped at - 50 mV. The outward currents were reduced when GTP was excluded from the intracellular recording solution or when GDP-beta-S was added. 8-Bromo cyclic AMP (5 mmol/1) neither produced an effect per se nor affected the 5-HT-induced outward current in A9 cells, thus excluding cAMP as a second messenger involved in 5-HT1C receptor activation. Phorbol myristic acetate (PMA; 10 mumol/1) did not affect the electrical activity of the transfected A9 cells but reduced the 5-HT-induced current amplitude to 71+/-9% of the control value (n = 12). This indicates that activation of protein kinase C does not play a direct role in the 5-HT-induced response in these cells. The 5-HT induced currents mainly involved potassium ions, although a small contribution of chloride ions was also observed. The 5-HT-induced current was inhibited by the K+ channel blocking agents tetraethylammonium (1 mmol/1), apamin (0,5 mumol/1) and 4-aminopyridine (5 mmol/1). The 5-HT-induced currents recorded at - 50 mV were unaffected by removal of extracellular calcium, but inclusion of the calcium chelator BAPTA (5 mmol/1) in the intracellular solutions abolished the current. Measurement with the calcium indicator Fluo-3 revealed a 5-HT-induced increase in intracellular calcium which was not affected by removal of extracellular calcium but declined after repeated stimulation. Determinated of pD2 and K(B) values of several 5-HT ligands using Fura-2 calcium measurements confirmed the pharmacology of the 5-HTc receptor. The results show that cloned rat 5-HT1C receptors expressed in A9 cells activate a calcium-dependent potassium conductance. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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