Tetrodotoxin-sensitive component of sodium gating current in squid giant axons

$68 COMPARISON OF RESPONSIVENESS OF POA NEURONS AND OVLT NEURONS TO PGE2. TAKUJI MATSUDA, TOSHIHIRO NAKASHIMA, TETSURO HORI AND EAZUFUMI KURIYAMA, Department of P h y s i o l o g y , Saga Medical School, Saga, 840-01, J a p a n It has n o t y e t been d e t e r m i n e d how b l o o d - b o r n e endogenous p y r o g e n s (EPs) such as 1L-l, i n t e r f e r o n s and TNF, e v e n t u a l l y r e a c h o r o t h e r w i s e s i g n a l t h e i r r e c e p t o r s in the b r a i n . Recent s t u d i e s s u g g e s t c r i t i c a l r o l e s o f organum v a s c u l o s u m lamina t e r m i n a l i s (OVLT) f o r f i b r e g e n c s i s , as the e n t r y s i t e s of EPs or t h e i r a c t i v e f r a g m e n t or as s i t e s of s i g n a l t r a n s d u c t i o n of EPs i n t o second m e s s e n g e r s l i k e p r o s t a g l a n d i n s . To examine the l a t t e r p o s s i b i l i t y , we i n v e s t i g a t e d the e f f e c t s of p r o s t a g l a n d i n E2 (PGEe), one of the most p r o m i s i n g c a n d i d a t e s f o r t h e f i n a l m e d i a t o r of f e v e r , on t h e a c t i v i t y of n e u r o n s in t i s s u e s l i c e s of r a t OVLT and POA. S i n c e r e p e a t e d a p p l i c a t i o n s of PGE2 at s h o r t i n t e r v a l s r e s u l t s in t a c h y p h y l a x i s , we a p p l i e d i t on t h e n e u r o n s at i n t e r v a l s l o n g e r t h a n 15-30 min. About 70% of 48 OVLT n e u r o n s and 70% of 33 POA n e u r o n s r e sponded to l o c a l p e r f u s i o n w i t h PGE2 (lpM-lnM). Neuronal r e s p o n s e s were r e t a i n e d a f t e r s y n a p t i c b l o c k a d e , s u g g e s t i n g p o s t s y n a p t i e a c t i o n of PGE2. The r e s p o n s e of OVLT n e u r o n s to l o c a l p e r f u s i o n with PGE2 d i f f e r e d from t h a t of POA n e u r o n s , as f o l l o w s : 1) The t h r e s h o l d d o s e of PGE2 to p r o d u c e c h a n g e s in n e u r o n a l a c t i v i t y was s i g n i f i c a n t l y lower in t h e OVLT n e u r o n s . This is c o m p a t i b l e w i t h the p r e v i o u s o b s e r v a t i o n t h a t OVLT i s more s e n s i t i v e t h a n POA to m i c r o i n j e c t e d PGE2 in p r o d u c i n g f e v e r . 2) F i f t e e n of 48 OVLT n e u r o n s e x h i b i t e d s l o w e r o n s e t ( l a t e n c y 4-16 min) and l o n g e r (more t h a n 30 min) d u r a t i o n , which were not o b s e r v e d among POA n e u r o n s . 3) The m a j o r i t y of w a r m - s e n s i t i v e n e u r o n s in t h e OVLT d e c r e a s e d a c t i v i t y on a p p l i c a t i o n of PGEe, b u t t h e r e was no c o r r e l a t i o n between thermal r e s p o n s i v e n e s s and r e s p o n s e to PGE2 f o r POA n e u r o n s .