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Possible function of SP on the adrenal gland
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POSSIBLE FUNCTION OF SP ON THE ADRENAL GLAND P. OEHME, K. NIEBER, A. HINENKO, I .
ROSKE and R. RATHSACK
Institute o f Drug R e s e a r c h , Academy of S c i e n c e s of t h e GDR, Alfred-Kowalke-Str. 4, B e r l i n 1136, GDR The a d r e n a l g l a n d p l a y s e p r i n c i p a l r o l e i n t h e mechanisms of stress-induced disorders. I n the a d r e n a l g l a n d a c o - l o c a l i z a t i o n of s u b s t a n c e P (SP) was d e s c r i b e d w i t h i n the e n d i n g s of s p l a n c h n i c nerve and cellular e i e m e n t s . Because SP i s i n v o l v e d i n s t r e s s r e s p o n ses i t may be p o s s i b l e t h a t t h e " a n t i - s t r e s s - e f f e c t " o f SP i s m e d i a t e d by r e g u l a t i o n of the c a t e c h o l a m i n e s e c r e t i o n i n the adrenals, SP i n h i b i t e d t h e n i c o t i n e - e v o k e d r e l e a s e o f 3H-NA i n a dosed e p e n d e n t manner i n d i c a t i n g a p o s t s y n a p t i c a c t i o n of SP i n the c h o l i n e r g i c - a d r e n e r g t c interaction. SP a I s o i n h i b i t e d t h e s t i m u l a t e d ~H-ACh o u t f l o w ( e l e c t r i c a l field stimuiation), This effect reflects a presynaptic a c t i o n o f SP, Furth~r91nvestigations u s i n g the SP a n t a g o n i s t , D-Pro 2, D - T r p ' -SP or the s t r u c t u r a l l y related tetrapeptide tufts i n i n d i c a t e d t h a t the p r e s y n a p t i c a c t i o n may be r e a l i z e d by s e q u e n c e - s p e c i f i c r e c e p t o r s , whereas the p o s t s y n a p t i c a c t i o n may be r e a l i z e d by m o d i f i c a t i o n of the s e n s i t i v i t y of nicotinic receptors, The mechanism o f d e p l e t i o n by SP o f i n o s i t o l phospholipids i n t h e e n v i r o n m e n t may have p h y s i o l o g i c a l r e l e v a n c e f o r the inhibition of the c a t e c h o l a m i n e s e c r e t i o n i n the a d r e n a l medulla, Exposure to SP (20 s) decreased the 32p incorporation into ~ inositol phospholipids. During 5 mln exposure to GP the incorporation into phosphatidylinositol-4,5bisphosphate returned up to the control level, whereas that into the phosphatidylchoIine or phosphatldylserine fraction strongly decreased. The detaiied mechanism accordin 0 to which SP modulates the catecholamine release is not known. It may be possible that SP controls the Ca 2+ level by regulating inosltol phospholipid hydrolysis. The results indicate that SP only acts in situations of increased sympathetic nerve activity foiIowed by an increased release of catecholamines. On the other hand SP(I-4) also induced marked inhibition of both the 3H-ACh and ~H-NA release indicating that the inhlbitory effect on the pre- 8nd postsynaptic action does not require the complete sequence of the BP moiecule. The N-terminus of the SP molecule is the essential nucleus for the "anti-stress-effect" of SP. The implications of ~2-adrenoceptors in the realization of the SP-induced regulation of the catecholanine imba!ance is considered.
POSSIBLE FUNCTION OF SP ON THE ADRENAL GLAND P. OEHME, K. NIEBER, A. HINENKO, I .
ROSKE and R. RATHSACK
Institute o f Drug R e s e a r c h , Academy of S c i e n c e s of t h e GDR, Alfred-Kowalke-Str. 4, B e r l i n 1136, GDR The a d r e n a l g l a n d p l a y s e p r i n c i p a l r o l e i n t h e mechanisms of stress-induced disorders. I n the a d r e n a l g l a n d a c o - l o c a l i z a t i o n of s u b s t a n c e P (SP) was d e s c r i b e d w i t h i n the e n d i n g s of s p l a n c h n i c nerve and cellular e i e m e n t s . Because SP i s i n v o l v e d i n s t r e s s r e s p o n ses i t may be p o s s i b l e t h a t t h e " a n t i - s t r e s s - e f f e c t " o f SP i s m e d i a t e d by r e g u l a t i o n of the c a t e c h o l a m i n e s e c r e t i o n i n the adrenals, SP i n h i b i t e d t h e n i c o t i n e - e v o k e d r e l e a s e o f 3H-NA i n a dosed e p e n d e n t manner i n d i c a t i n g a p o s t s y n a p t i c a c t i o n of SP i n the c h o l i n e r g i c - a d r e n e r g t c interaction. SP a I s o i n h i b i t e d t h e s t i m u l a t e d ~H-ACh o u t f l o w ( e l e c t r i c a l field stimuiation), This effect reflects a presynaptic a c t i o n o f SP, Furth~r91nvestigations u s i n g the SP a n t a g o n i s t , D-Pro 2, D - T r p ' -SP or the s t r u c t u r a l l y related tetrapeptide tufts i n i n d i c a t e d t h a t the p r e s y n a p t i c a c t i o n may be r e a l i z e d by s e q u e n c e - s p e c i f i c r e c e p t o r s , whereas the p o s t s y n a p t i c a c t i o n may be r e a l i z e d by m o d i f i c a t i o n of the s e n s i t i v i t y of nicotinic receptors, The mechanism o f d e p l e t i o n by SP o f i n o s i t o l phospholipids i n t h e e n v i r o n m e n t may have p h y s i o l o g i c a l r e l e v a n c e f o r the inhibition of the c a t e c h o l a m i n e s e c r e t i o n i n the a d r e n a l medulla, Exposure to SP (20 s) decreased the 32p incorporation into ~ inositol phospholipids. During 5 mln exposure to GP the incorporation into phosphatidylinositol-4,5bisphosphate returned up to the control level, whereas that into the phosphatidylchoIine or phosphatldylserine fraction strongly decreased. The detaiied mechanism accordin 0 to which SP modulates the catecholamine release is not known. It may be possible that SP controls the Ca 2+ level by regulating inosltol phospholipid hydrolysis. The results indicate that SP only acts in situations of increased sympathetic nerve activity foiIowed by an increased release of catecholamines. On the other hand SP(I-4) also induced marked inhibition of both the 3H-ACh and ~H-NA release indicating that the inhlbitory effect on the pre- 8nd postsynaptic action does not require the complete sequence of the BP moiecule. The N-terminus of the SP molecule is the essential nucleus for the "anti-stress-effect" of SP. The implications of ~2-adrenoceptors in the realization of the SP-induced regulation of the catecholanine imba!ance is considered.