EFFECT OF ENDOTHELIN-1, ENDOTHELIN-3 AND C-TERMINAL HEXAPEPTIDE, ENDOTHELIN (16-21) ON MOTOR-ACTIVITY IN RATS

Intracerebroventricular administration of ET-1 (12.5 and 25 pmol/rat) and ET-3 (25 and 50 pmol/rat) induced the loss of the righting reflex and barrel-rolling behaviour in rats. The C-terminal hexapeptide ET(16-21) did not produce these effects. The automated recording of motor activity revealed that, unlike ET(16-21), both ET-1 and ET-3 evoke a dose-regulated increase of the immobility time. Pretreatment with peptidase inhibitors did not modify the activity of subthreshold doses of peptides. Since ET(16-21) displays full agonist properties at ETb but does not interact with ETa receptors, the present data suggest that the behavioural syndrome induced by centrally administered ET-1 and ET-3 may be mediated by stimulation of ETa receptors. © 1990.