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Response of brain and pituitary pools of dynorphin as compared to vasopressin to acute stress in the rat
Life Sciences, Vol. 33, Sup. I, 1983, pp. 29-32 Printed in the U.S.A.
Pergamon Press
R E S P O N S E OF B R A I N A N D P I T U I T A R Y POOLS OF D Y N O R P H I N AS C O M P A R E D TO V A S O P R E S S I N TO A C U T E S T R E S S IN THE RAT M.J.
Millan,
M.H.
Millan,
Y.F.
T s a n g and A. Herz
D e p a r t m e n t of N e u r o p h a r m a c o l o g y , M a x - P l a n c k - I n s t i t u t fur P s y c h i a t r i e , K r a e p e l i n s t r a s s e 2, D - 8 O O O M H n c h e n 40 F e d e r a l R e p u b l i c of G e r m a n y (Received in final form June 26, 1983) Summary 5 min f o o t - s h o c k r e s u l t e d in an e l e v a t i o n in l e v e l s of i m m u n o r e a c t i v e ( i r ) - d y n o r p h i n (DYN) and i r - v a s o p r e s s i n (VP) in the h y p o t h a l a m u s w h e r e a s their l e v e l s w e r e not s i g n i f i c a n t l y m o d i f i e d in the n e u r o i n t e r m e d i a t e p i t u i t a r y . In the a n t e r i o r p i t u i t a r y , however, a fall in i r - D Y N in the a b s e n c e of any c h a n g e in ir-VP was detected. F u r t h e r , in the t h a l a m u s and m e d u l l a / p o n s , resp e c t i v e l y , a d e c r e a s e and i n c r e a s e in levels of ir-VP was o b s e r v e d w h i l s t the c o n t e n t of i r - D Y N t h e r e i n was not s i g n i f i c a n t l y a f f e c t e d . T h e s e f i n d i n g s s u p p o r t the c o n c e p t of a c o m m o n o r i g i n and c o - m o d u l a t i o n of D Y N and VP in the h y p o t h a l a m i c n e u r a l lobe axis and that, e x t r i n s i c to this, DYN and VP are l o c a l i z e d and m o d u l a t e d i n d e p e n d e n t l y of each other. In a d d i t i o n to v a s o p r e s s i n (VP) and o x y t o c i n , the n e u r o h y p o p h y s e a l t r a c t r u n n i n g f r o m the m a g n o c e l l u l a r p a r a v e n t r i c u l a r and s u p r a o p t i c n u c l e i of the h y p o t h a l a m u s to the n e u r a l lobe, c o n t a i n s o p i o i d p e p t i d e s of the p r o - d y n o r p h i n f a m i l y such as d y n o r p h i n (DYN) and ~ - n e o - e n d o r p h i n . D a t a e v i d e n t i a l of a c o - l o c a l i z a t i o n of these w i t h VP (but not oxytocin) t h e r e i n and of a cor e g u l a t i o n of t h e i r r e l e a s e f r o m n e u r a l lobe t e r m i n a l s has been a c q u i r e d (I-4). However, r e c e n t s t u d i e s have i n d i c a t e d that such an i n t e r - r e l a t i o n s h i p of DYN w i t h VP m a y be l i m i t e d to this axis and does not o c c u r in e x t r a - h y p o t h a l a m i c CNS tissues, in w h i c h V P - c o n t a i n i n g n e u r o n s d e r i v e d f r o m h y p o t h a l a m i c p o p u l a t i o n s of som a t a a r e present, or the a n t e r i o r p i t u i t a r y (3,5, M i l l a n in press) The p r e s e n t i n v e s t i g a t i o n f u r t h e r e x p l o r e s the r e l a t i o n s h i p of D Y N to V P in the h y p o t h a l a m i c - n e u r a l lobe axis as c o m p a r e d to o t h e r t i s s u e s by m e a n s of an e v a l u a t i o n of t h e i r c o m p a r a t i v e resp o n s e to a c u t e stress. S u c h a m a n i p u l a t i o n was c o n s i d e r e d a p p r o p r i a t e since t h e r e is e v i d e n c e that o p i o i d p e p t i d e s , i n c l u d i n g DYN, are i n v o l v e d in the r e s p o n s e to stress (6,7). Further, c e r t a i n p o o l s of VP may, s i m i l a r l y , be i n f l u e n c e d by i m p o s i t i o n of this or r e l a t e d s t i m u l i (8,9,10). Methods Male,
S p r a g u e - D a w l e y rats of
180-2OOg were decapitated either
0024-3205/83 $3.00 + .00 Copyright (c) 1983 Pergamon Press Ltd.
30
Interrelationship of VP and Opioids
Vol. 33, Sup. I, 1983
a f t e r r e m o v a l f r o m h o m e c a g e s (basal) or 10 or 60 m i n f o l l o w i n g 5 m i n f o o t - s h o c k (pulses of 3.5 mA, 300 m s e c d u r a t i o n , 30 p e r m i n ) . T h e p i t u i t a r y w a s d i v i d e d i n t o the a n t e r i o r l o b e (AL) a n d neurointermediate lobe (NIL) a n d the b r a i n i n t o the h y p o t h a l a m u s , t h a l a m u s , a n d m e d u l l a / p o n s . P r o c e d u r e s for r a d i o i m m u n o a s s a y of p e p t i d e s etc. a r e d e t a i l e d e l s e w h e r e (4,11). A n t i b o d i e s u s e d w e r e h i g h l y s p e c i f i c a n d s h o w e d no m u t u a l c r o s s - r e a c t i v i t y : t h a t to VP d i d n o t r e c o g n i z e o x y t o c i n a n d t h a t to D Y N d i d n o t b i n d D Y N I _ 8 , ~ - n e o - e n d o r p h i n , D Y N B or l e u - e n k e p h a l i n (see 4 , 1 1 ) . Results As s h o w n in T a b l e I, i r - D Y N a n d i r - V P r e v e a l e d s i m i l a r p a t t e r n s of d a t a as c o n c e r n s the h y p o t h a l a m u s a n d NIL. In the f o r m e r , l e v e l s of b o t h s h o w e d an e l e v a t i o n a c h i e v i n g s t a t i s t i c a l s i g n i f i c a n c e at 60 m i n . , w h e r e a s in t h e N I L no s i g n i f i c a n t a l t e r a t i o n was seen. H o w e v e r , in o t h e r s t r u c t u r e s , i r - D Y N a n d i r - V P m a n i f e s t e d c o n t r a s t i n g p a t t e r n s of d a t a (Table II). In the AL, at 10 m i n . , a d e p r e s s i o n in i r - D Y N w a s s e e n w h i l s t i r - V P t e n d e d to rise. F u r t h e r , in the t h a l a m u s , in d i s t i n c t i o n to the l a c k of c h a n g e in i r - D Y N , a d i m i n u t i o n in i r - V P w a s o b s e r v e d . F i n a l l y , in the m e d u l l a / p o n s , in c o n t r a s t to i r - D Y N , l e v e l s of i r - V P w e r e e l e v a t e d . TABLE
I
Hypothalamus
Neurointermediate
lobe
ir-DYN
ir-VP
ir-DYN
ir-VP
Basal n=9
34.4 +1.7
3121.7 +264.2
1432.6 +142.2
2907.3 +412.5
10 m i n n=10
40.7 +2.9
3794.8 +211.3
1392.6 +91.4
3030.6 +315.O
60 m i n n=10
41.8" +2.1
4080.6** +219.2
1296.4 +72.5
2635.9 +251.3
T h e I n f l u e n c e of F o o t - s h o c k S t r e s s u p o n I m m u n o r e a c t i v e ( i r ) - D y n o r p h i n (DYN) a n d - V a s o p r e s s i n (VP)in the H y p o thalamic-neurohypophyseal Axis. * p
lobe
II Thalamus
Medulla/pons
ir-DYN
ir-VP
ir-DYN
ir-VP
ir-DYN
ir-VP
Basal n=9
194.2 +13.2
30.6 +8.4
5.8 +0.3
6.2 +0.4
9.8 +0.8
2.5 +0.2
10 m i n n=10
139.2"* +12.1
35.6 +7.1
6.2 +0.4
4.7** +0.3
10.O +0.6
3.3 +0.3
60 m i n n=10
149.3 +19.4
28.6 +9.1
6.0 +0.5
4.9* 0.2
9.6 +0.9
3.6** +0.2
T h e i n f l u e n c e of F o o t - s h o c k S t r e s s u p o n I m m u n o r e a c t i v e ( i r ) - D y n o r p h i n (DYN) a n d - V a s o p r e s s i n (VP) in the A n t e r i o r P i t u i t a r y a n d E x t r a - h y p o t h a l a m i c T i s s u e s of B r a i n . * P < O . O 5 **p
Vol. 33, Sup. I, 1983
Interrelationship
of VP and Opioids
31
Discussion The p r e s e n t data c o n c e r n i n g i r - D Y N are in line w i t h our p r e v i o u s r e p o r t (see ref. 6). Studies e m p l o y i n g s p e c i f i c r a d i o i m m u n o a s s a y s have i n d i c a t e d that, in the rat, n e u r o h y p o p h y s e a l pools of ir-VP are not a f f e c t e d by p h y s i c a l or e m o t i o n a l s t r e s s o r s such as f o o t - s h o c k (12-16). The p r e s e n t d a t a are in a g r e e m e n t in failing to d e t e c t a s i g n i f i c a n t i n f l u e n c e of f o o t - s h o c k upon NIL stores of ir-VP. In the h y p o t h a l a m u s , however, a rise in the content of ir-VP was observed. In fact, in line w i t h this finding, 5 m i n i m m o b i l i z a t i o n stress has been o b s e r v e d to r e s u l t in an inc r e a s e in levels of ir-VP in the p a r a v e n t r i c u l a r n u c l e u s (8). Perh a p s the m o s t c o n s e r v a t i v e i n t e r p r e t a t i o n of the p r e s e n t i n c r e a s e is an e n h a n c e m e n t in the s y n t h e s i s of VP w h i c h w o u l d not be ref l e c t e d in the N I L or o t h e r tissues in v i e w of the slow rate of a x o n a l flow of V P (14). The increase in c o n t e n t of ir-VP in the m e d u l l a / p o n s m i g h t r e p r e s e n t a r e d u c t i o n in the r e l e a s e of ir-VP therein. T h e s e m e d u l l a / p o n s pools of ir-VP are d e r i v e d from the p a r a v e n t r i c u l a r n u c l e u s in c o n t r a s t to those in the t h a l a m u s der i v e d f r o m the s u p r a c h i a s m a t i c n u c l e u s (16,17). This d i f f e r e n t i a l o r i g i n m a y r e l a t e to the c o n t r a s t i n g d e c r e a s e in t h a l a m i c ir-VP u n d e r stress. T h e s e d a t a e x t e n d r e p o r t s of the r e s p o n s e of disc r e t e b r a i n pools of ir-VP to such stimuli as shock, h a e m m o r r h a g e or o s m o t i c c h a l l a n g e (10,18,19,20,21). O b s e r v a t i o n s of d i f f e r e n t i a l e f f e c t s upon b r a i n as c o m p a r e d to N I L stores should be c o n s i d e r e d in the light of e v i d e n c e that i n d e p e n d e n t p o p u l a t i o n s of h y p o t h a l a m i c V P - s y n t h e s i z i n g s o m a t a p r o j e c t to e i t h e r the n e u r a l lobe or p a r t i c u l a r CNS r e g i o n s (16). In the case of the h y p o t h a l a m u s and NIL, i r - D Y N and ir-VP d i s p l a y e d s i m i l a r p a t t e r n of data u n d e r stress, in line w i t h p r e v i o u s f i n d i n g s of a p a r a l l e l i n f l u e n c e upon i r - D Y N and ir-VP in the h y p o t h a l a m i c - n e u r o h y p o p h y s e a l axis of g l u c o c o r t i c o i d m a n i p u l a tions, d e h y d r a t i o n or d e s t r u c t i o n of a s c e n d i n g n o r a d r e n e r g i c n e t w o r k s in the b r a i n (4, Millan, in press). However, in the AL, t h a l a m u s and m e d u l l a / p o n s , d i f f e r e n t i a l e f f e c t s of stress upon i r - D Y N as c o m p a r e d to ir-VP w e r e d e t e c t e d s i m i l a r l y in line w i t h our s t u d i e s of the m o d u l a t i o n of these p o o l s (5, Millan, in press). Further, n e u r o a n a t o m i c a l studies have i n d i c a t e d a c o m m o n o r i g i n and c o - o c c u r e n c e of DYN w i t h VP in the n e u r o h y p o p h y s e a l tract but an i n d e p e n d e n t l o c a l i z a t i o n e l s e w h e r e (3,5,22, Millan, in press). Thus, the p r e s e n t d a t a s u p p o r t the c o n c e p t of a c o - l o c a l i z a t i o n a n d c o - m o d u l a t i o n of DYN and VP in the h y p o t h a l a m i c - n e u r o h y p o p h y seal axis but, e x t r i n s i c to this, in the A L and e x t r a h y p o t h a l a m i c b r a i n tissues, an i n d e p e n d e n t l o c a l i z a t i o n and m o d u l a t i o n of DYN as c o m p a r e d to VP. Acknowledgement M.J. M i l l a n was schaft, Bonn.
supported
by the D e u t s c h e
Forschungsgemein-
References I .
S.J. WATSON, H. AKIL, W. FISCHLI, A. G O L D S T E I N , E. ZIMMERMAN, G. N I L A V E R and T.B. V A N W I M E R S M A G R E I D A N U S , S c i e n c e 216, 8587 (1982).
32
2.
3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.
15. 16.
17. 18. 19. 20. 21. 22.
Interrelationship
of VP and Opioids
Vol. 33, Sup. I, 1983
E. WEBER, C.J. EVANS, J.D. BARCHAS. In R e g u l a t o r y Peptides: from M o l e c u l a r B i o l o g y to Function. Eds., E. Costa and M. Trabucchi, pp 519-525, R a v e n Press, N e w York (1982). M.J. MILLAN, M.H. M I L L A N and A. HERZ, N e u r o e n d o c r i n o l o g y 36, 310-319 (1983). V. HOLLT, I. HAARMAN, B.R. S E I Z I N G E R and A. HERZ, N e u r o e n d o c r i n o l o g y 33, 333-339 (1981). M.H. MILLAN, M.J. M I L L A N and A. HERZ, N e u r o s c i . Lett. 35, 165-169 (1982). M.J. MILLAN, Y.F. TSANG, R. P R Z E W L O C K I , V. H O L L T and A. HERZ, N e u r o s c i . Lett. 2_!4, 75-79. (1981). M.J. MILLAN, Mod. Probl. P h a r m a c o p s y c h i a t r y 17, 49-67 (1981). B. KRISCH, Cell. Tiss. Res. 189, 269-275. (1978). A . N E G R O - V I L A R and J. SAAVEDRA, B r a i n Res. Bull. 5, 353-358 (1980). N.W. K A S T I N G and J.B. MARTIN, B r a i n Res. 258, 127-132 (1983). E. WEBER, C.J. EVANS and J.D. BARCHAS, Nature, 299 77-79 (1982) W. KNEPEL, D. N U T T O and G. H E R T T I N G , N e u r o e n d o c r i n o l o g y 34, 353-356 (1982). M.K. HUSAIN, W.M. MANGER, T.W. ROCK, R.J. W E I S S and A.G. FRANTZ, E n d o c r i n o l o g y 104, 641-644 (1979). C.R.W. EDWARDS, In C l i n i c a l N e u r o e n d o c r i n o l o g y Vol I, Eds., L. M a r t i n i and G.M. Besser, pp 527-567, A c a d e m i c Press, N e w York (1977). L.C. KEIL and W.B. SEVERS, E n d o c r i n o l o g y 1OO, 30-38. (1977). M.V. S O F R O N I E W and A. WEINDL, In E n d o g e n o u s P e p t i d e s and Learn i n g and M e m o r y P r o c e s s e s , Eds. J.L. M a r t i n e z , R.A. Jensen, R.B. Messing, H. R i g t e r and J.L. McGaugh, pp 327-369, Academic Press, N e w Y o r k (1981). S. T A L L A K S E N , S. J O S E P H and K. KNIGGE, N e u r o s c i . Abstr. 8, 808 (1982). Q.J. PITTMAN, W.L. V E A L E and K. LEDERIS, P e p t i d e s 3, 5 1 5 - 5 2 0 (1982). R.C. WANG, L. SHARE, J.T. C R O F T O N and T. KIMURA, N e u r o e n d o c r i n o l o g y 33, 61-66 (1982). M. CASTEL, N. SIVAN, R. DAVID, Y. E P S T E I N and S. GLICK, Neurosci. Lett. Suppl. 9, $537 (1982). R.L. ZERBE, M. P A L K O V I T S and I.J. KOPIN, Clin. Res. 30 413A (1982). S.J. W A T S O N , H. K H A C H A T U R I A N , H. AKIL, D.H. COY, and A. G O L D S T E I N , S c i e n c e 218, 1134-1136 (1982).
Pergamon Press
R E S P O N S E OF B R A I N A N D P I T U I T A R Y POOLS OF D Y N O R P H I N AS C O M P A R E D TO V A S O P R E S S I N TO A C U T E S T R E S S IN THE RAT M.J.
Millan,
M.H.
Millan,
Y.F.
T s a n g and A. Herz
D e p a r t m e n t of N e u r o p h a r m a c o l o g y , M a x - P l a n c k - I n s t i t u t fur P s y c h i a t r i e , K r a e p e l i n s t r a s s e 2, D - 8 O O O M H n c h e n 40 F e d e r a l R e p u b l i c of G e r m a n y (Received in final form June 26, 1983) Summary 5 min f o o t - s h o c k r e s u l t e d in an e l e v a t i o n in l e v e l s of i m m u n o r e a c t i v e ( i r ) - d y n o r p h i n (DYN) and i r - v a s o p r e s s i n (VP) in the h y p o t h a l a m u s w h e r e a s their l e v e l s w e r e not s i g n i f i c a n t l y m o d i f i e d in the n e u r o i n t e r m e d i a t e p i t u i t a r y . In the a n t e r i o r p i t u i t a r y , however, a fall in i r - D Y N in the a b s e n c e of any c h a n g e in ir-VP was detected. F u r t h e r , in the t h a l a m u s and m e d u l l a / p o n s , resp e c t i v e l y , a d e c r e a s e and i n c r e a s e in levels of ir-VP was o b s e r v e d w h i l s t the c o n t e n t of i r - D Y N t h e r e i n was not s i g n i f i c a n t l y a f f e c t e d . T h e s e f i n d i n g s s u p p o r t the c o n c e p t of a c o m m o n o r i g i n and c o - m o d u l a t i o n of D Y N and VP in the h y p o t h a l a m i c n e u r a l lobe axis and that, e x t r i n s i c to this, DYN and VP are l o c a l i z e d and m o d u l a t e d i n d e p e n d e n t l y of each other. In a d d i t i o n to v a s o p r e s s i n (VP) and o x y t o c i n , the n e u r o h y p o p h y s e a l t r a c t r u n n i n g f r o m the m a g n o c e l l u l a r p a r a v e n t r i c u l a r and s u p r a o p t i c n u c l e i of the h y p o t h a l a m u s to the n e u r a l lobe, c o n t a i n s o p i o i d p e p t i d e s of the p r o - d y n o r p h i n f a m i l y such as d y n o r p h i n (DYN) and ~ - n e o - e n d o r p h i n . D a t a e v i d e n t i a l of a c o - l o c a l i z a t i o n of these w i t h VP (but not oxytocin) t h e r e i n and of a cor e g u l a t i o n of t h e i r r e l e a s e f r o m n e u r a l lobe t e r m i n a l s has been a c q u i r e d (I-4). However, r e c e n t s t u d i e s have i n d i c a t e d that such an i n t e r - r e l a t i o n s h i p of DYN w i t h VP m a y be l i m i t e d to this axis and does not o c c u r in e x t r a - h y p o t h a l a m i c CNS tissues, in w h i c h V P - c o n t a i n i n g n e u r o n s d e r i v e d f r o m h y p o t h a l a m i c p o p u l a t i o n s of som a t a a r e present, or the a n t e r i o r p i t u i t a r y (3,5, M i l l a n in press) The p r e s e n t i n v e s t i g a t i o n f u r t h e r e x p l o r e s the r e l a t i o n s h i p of D Y N to V P in the h y p o t h a l a m i c - n e u r a l lobe axis as c o m p a r e d to o t h e r t i s s u e s by m e a n s of an e v a l u a t i o n of t h e i r c o m p a r a t i v e resp o n s e to a c u t e stress. S u c h a m a n i p u l a t i o n was c o n s i d e r e d a p p r o p r i a t e since t h e r e is e v i d e n c e that o p i o i d p e p t i d e s , i n c l u d i n g DYN, are i n v o l v e d in the r e s p o n s e to stress (6,7). Further, c e r t a i n p o o l s of VP may, s i m i l a r l y , be i n f l u e n c e d by i m p o s i t i o n of this or r e l a t e d s t i m u l i (8,9,10). Methods Male,
S p r a g u e - D a w l e y rats of
180-2OOg were decapitated either
0024-3205/83 $3.00 + .00 Copyright (c) 1983 Pergamon Press Ltd.
30
Interrelationship of VP and Opioids
Vol. 33, Sup. I, 1983
a f t e r r e m o v a l f r o m h o m e c a g e s (basal) or 10 or 60 m i n f o l l o w i n g 5 m i n f o o t - s h o c k (pulses of 3.5 mA, 300 m s e c d u r a t i o n , 30 p e r m i n ) . T h e p i t u i t a r y w a s d i v i d e d i n t o the a n t e r i o r l o b e (AL) a n d neurointermediate lobe (NIL) a n d the b r a i n i n t o the h y p o t h a l a m u s , t h a l a m u s , a n d m e d u l l a / p o n s . P r o c e d u r e s for r a d i o i m m u n o a s s a y of p e p t i d e s etc. a r e d e t a i l e d e l s e w h e r e (4,11). A n t i b o d i e s u s e d w e r e h i g h l y s p e c i f i c a n d s h o w e d no m u t u a l c r o s s - r e a c t i v i t y : t h a t to VP d i d n o t r e c o g n i z e o x y t o c i n a n d t h a t to D Y N d i d n o t b i n d D Y N I _ 8 , ~ - n e o - e n d o r p h i n , D Y N B or l e u - e n k e p h a l i n (see 4 , 1 1 ) . Results As s h o w n in T a b l e I, i r - D Y N a n d i r - V P r e v e a l e d s i m i l a r p a t t e r n s of d a t a as c o n c e r n s the h y p o t h a l a m u s a n d NIL. In the f o r m e r , l e v e l s of b o t h s h o w e d an e l e v a t i o n a c h i e v i n g s t a t i s t i c a l s i g n i f i c a n c e at 60 m i n . , w h e r e a s in t h e N I L no s i g n i f i c a n t a l t e r a t i o n was seen. H o w e v e r , in o t h e r s t r u c t u r e s , i r - D Y N a n d i r - V P m a n i f e s t e d c o n t r a s t i n g p a t t e r n s of d a t a (Table II). In the AL, at 10 m i n . , a d e p r e s s i o n in i r - D Y N w a s s e e n w h i l s t i r - V P t e n d e d to rise. F u r t h e r , in the t h a l a m u s , in d i s t i n c t i o n to the l a c k of c h a n g e in i r - D Y N , a d i m i n u t i o n in i r - V P w a s o b s e r v e d . F i n a l l y , in the m e d u l l a / p o n s , in c o n t r a s t to i r - D Y N , l e v e l s of i r - V P w e r e e l e v a t e d . TABLE
I
Hypothalamus
Neurointermediate
lobe
ir-DYN
ir-VP
ir-DYN
ir-VP
Basal n=9
34.4 +1.7
3121.7 +264.2
1432.6 +142.2
2907.3 +412.5
10 m i n n=10
40.7 +2.9
3794.8 +211.3
1392.6 +91.4
3030.6 +315.O
60 m i n n=10
41.8" +2.1
4080.6** +219.2
1296.4 +72.5
2635.9 +251.3
T h e I n f l u e n c e of F o o t - s h o c k S t r e s s u p o n I m m u n o r e a c t i v e ( i r ) - D y n o r p h i n (DYN) a n d - V a s o p r e s s i n (VP)in the H y p o thalamic-neurohypophyseal Axis. * p
lobe
II Thalamus
Medulla/pons
ir-DYN
ir-VP
ir-DYN
ir-VP
ir-DYN
ir-VP
Basal n=9
194.2 +13.2
30.6 +8.4
5.8 +0.3
6.2 +0.4
9.8 +0.8
2.5 +0.2
10 m i n n=10
139.2"* +12.1
35.6 +7.1
6.2 +0.4
4.7** +0.3
10.O +0.6
3.3 +0.3
60 m i n n=10
149.3 +19.4
28.6 +9.1
6.0 +0.5
4.9* 0.2
9.6 +0.9
3.6** +0.2
T h e i n f l u e n c e of F o o t - s h o c k S t r e s s u p o n I m m u n o r e a c t i v e ( i r ) - D y n o r p h i n (DYN) a n d - V a s o p r e s s i n (VP) in the A n t e r i o r P i t u i t a r y a n d E x t r a - h y p o t h a l a m i c T i s s u e s of B r a i n . * P < O . O 5 **p
Vol. 33, Sup. I, 1983
Interrelationship
of VP and Opioids
31
Discussion The p r e s e n t data c o n c e r n i n g i r - D Y N are in line w i t h our p r e v i o u s r e p o r t (see ref. 6). Studies e m p l o y i n g s p e c i f i c r a d i o i m m u n o a s s a y s have i n d i c a t e d that, in the rat, n e u r o h y p o p h y s e a l pools of ir-VP are not a f f e c t e d by p h y s i c a l or e m o t i o n a l s t r e s s o r s such as f o o t - s h o c k (12-16). The p r e s e n t d a t a are in a g r e e m e n t in failing to d e t e c t a s i g n i f i c a n t i n f l u e n c e of f o o t - s h o c k upon NIL stores of ir-VP. In the h y p o t h a l a m u s , however, a rise in the content of ir-VP was observed. In fact, in line w i t h this finding, 5 m i n i m m o b i l i z a t i o n stress has been o b s e r v e d to r e s u l t in an inc r e a s e in levels of ir-VP in the p a r a v e n t r i c u l a r n u c l e u s (8). Perh a p s the m o s t c o n s e r v a t i v e i n t e r p r e t a t i o n of the p r e s e n t i n c r e a s e is an e n h a n c e m e n t in the s y n t h e s i s of VP w h i c h w o u l d not be ref l e c t e d in the N I L or o t h e r tissues in v i e w of the slow rate of a x o n a l flow of V P (14). The increase in c o n t e n t of ir-VP in the m e d u l l a / p o n s m i g h t r e p r e s e n t a r e d u c t i o n in the r e l e a s e of ir-VP therein. T h e s e m e d u l l a / p o n s pools of ir-VP are d e r i v e d from the p a r a v e n t r i c u l a r n u c l e u s in c o n t r a s t to those in the t h a l a m u s der i v e d f r o m the s u p r a c h i a s m a t i c n u c l e u s (16,17). This d i f f e r e n t i a l o r i g i n m a y r e l a t e to the c o n t r a s t i n g d e c r e a s e in t h a l a m i c ir-VP u n d e r stress. T h e s e d a t a e x t e n d r e p o r t s of the r e s p o n s e of disc r e t e b r a i n pools of ir-VP to such stimuli as shock, h a e m m o r r h a g e or o s m o t i c c h a l l a n g e (10,18,19,20,21). O b s e r v a t i o n s of d i f f e r e n t i a l e f f e c t s upon b r a i n as c o m p a r e d to N I L stores should be c o n s i d e r e d in the light of e v i d e n c e that i n d e p e n d e n t p o p u l a t i o n s of h y p o t h a l a m i c V P - s y n t h e s i z i n g s o m a t a p r o j e c t to e i t h e r the n e u r a l lobe or p a r t i c u l a r CNS r e g i o n s (16). In the case of the h y p o t h a l a m u s and NIL, i r - D Y N and ir-VP d i s p l a y e d s i m i l a r p a t t e r n of data u n d e r stress, in line w i t h p r e v i o u s f i n d i n g s of a p a r a l l e l i n f l u e n c e upon i r - D Y N and ir-VP in the h y p o t h a l a m i c - n e u r o h y p o p h y s e a l axis of g l u c o c o r t i c o i d m a n i p u l a tions, d e h y d r a t i o n or d e s t r u c t i o n of a s c e n d i n g n o r a d r e n e r g i c n e t w o r k s in the b r a i n (4, Millan, in press). However, in the AL, t h a l a m u s and m e d u l l a / p o n s , d i f f e r e n t i a l e f f e c t s of stress upon i r - D Y N as c o m p a r e d to ir-VP w e r e d e t e c t e d s i m i l a r l y in line w i t h our s t u d i e s of the m o d u l a t i o n of these p o o l s (5, Millan, in press). Further, n e u r o a n a t o m i c a l studies have i n d i c a t e d a c o m m o n o r i g i n and c o - o c c u r e n c e of DYN w i t h VP in the n e u r o h y p o p h y s e a l tract but an i n d e p e n d e n t l o c a l i z a t i o n e l s e w h e r e (3,5,22, Millan, in press). Thus, the p r e s e n t d a t a s u p p o r t the c o n c e p t of a c o - l o c a l i z a t i o n a n d c o - m o d u l a t i o n of DYN and VP in the h y p o t h a l a m i c - n e u r o h y p o p h y seal axis but, e x t r i n s i c to this, in the A L and e x t r a h y p o t h a l a m i c b r a i n tissues, an i n d e p e n d e n t l o c a l i z a t i o n and m o d u l a t i o n of DYN as c o m p a r e d to VP. Acknowledgement M.J. M i l l a n was schaft, Bonn.
supported
by the D e u t s c h e
Forschungsgemein-
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Vol. 33, Sup. I, 1983
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