NeuroAct Communication offers expert guidance to scientific communication.

  • Define a publication strategy: identify objectives, target audience, journals
  • Aid to effective presentation of pharmacological data
  • Experienced scientific writing and editing: research reports, posters, symposia

For more information Contact.
 

 

Differential ion current activation by human 5-HT1A receptors in Xenopus oocytes: evidence for agonist-directed trafficking of receptor signalling.

Heusler P, Pauwels PJ, Wurch T, Newman-Tancredi A, Tytgat J, Colpaert FC, Cussac D.
Neuropharmacology. 2005 Dec;49(7):963-76. Epub 2005 Jun 17.

The subject of the present study was the functional and pharmacological characterization of human 5-HT1A receptor regulation of ion channels in Xenopus oocytes. Activation of the heterologously expressed human 5-HT1A receptor induced two distinct currents in Xenopus oocytes, consisting of a smooth inward current (I(smooth)) and an oscillatory calcium-activated chloride current, I(Cl(Ca)). 5-HT1A receptor coupling to both ionic responses as well as to co-expressed inward rectifier potassium (GIRK) channels was pharmacologically characterized using 5-HT1A receptor agonists. The relative order of efficacy for activation of GIRK current was 5-HT approximately F13714 approximately L694,247 approximately LY228,729>flesinoxan approximately (+/-)8-OH-DPAT. In contrast, flesinoxan and (+/-)8-OH-DPAT typically failed to activate I(Cl(Ca)). The other ligands behaved as full or partial agonists, exhibiting an efficacy rank order of 5-HT approximately L694,247>F 13714 approximately LY228,729. The pharmacological profile of I(smooth) activation was completely distinct: flesinoxan and F13714 were inactive and rather exhibited an inhibition of this current. I(smooth) was activated by the other agonists with an efficacy order of L694,247>5-HT approximately LY228,729>(+/-)8-OH-DPAT. Moreover, activation of I(smooth) was not affected by application of pertussis toxin or the non-hydrolyzable GDP-analogue, guanosine-5'-O-(2-thio)-diphosphate (GDPbetaS), suggesting a GTP binding protein-independent pathway. Together, these results suggest the existence of distinct and agonist-specific signalling states of this receptor.