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Demonstration of histamine-sensitive adenylate cyclase in capillaries of guinea pig myocardium
49 79.
D E M O N S T R A T I O N OF H I S T A M I N E - S E N S I T I V E A D E N Y L ATE CYCLASE IN C A P I L L A R I E S OF G U I N E A PIG MYOCARDIUM. W. Schulze, A. W o l l e n b e r g e r . Centr. Inst. of Heart and Circul. Reg. Res., Acad. Sci. of the DDR, B e r l i n - B u c h , GDR. At p r e s e n t h i s t o c h e m i c a l and c y t o c h e m i c a l m e t h o d s are the sole means for d e m o n s t r a t i n g adenylate cyclase a c t i v i t y in the c a p i l l a r i e s of the coronary circulation. In our study sections of guinea pig v e n t r i c u l a r m u s c l e w e r e i n c u b a t e d in m e d i u m c o n t a i n i n g adenylyl i m i d o d i p h o s p h a t e as a fairly s p e c i f i c s u b s t r a t e of a d e n y l a t e cyclase and free lead ions at appr. 4x10 -5 M. E l e c t r o n dense reaction product, p r e s u m a b l y lead i m i d o d i p h o s p h a t e , was d e p o s i t e d in the m y o c a r d i a l cells at the s a r c o l e m m a and the T - t u b u l e s and in the c a p i l l a r i e s at the p l a s m a m e m b r a n e and p i n o c y t o t i c v e s i c l e s of the e n d o t h e l i a l cells. The r e a c t i o n in the c a p i l l a r i e s was m a r k e d l y e n h a n c e d by 10 -4 M h i s t a m i n e and this e n h a n c e m e n t was r e d u c e d by the H l - r e c e p t o r b l o c k e r m e p y r a m i n e (10 -5 M), but not by the H 2 - r e c e p t o r b l o c k e r b u r i m a m i d e (4x10 -4 M). The s t i m u l a t o r y effect of h i s t a m i n e on c y t o c h e m i c a l l y d e m o n s t r a b l e a d e n y l a t e cyclase in the e n d o t h e l i a l cells of the c a p i l l a r i e s may be an i n t e r m e d i a t e step in the a c t i o n of this amine on c a p i l l a r y p e r m e a b i l i t y in the heart.
80.
A N A E R O B I C C O N T R A C T I L E A C T I V I T Y AND M E T A B O L I C CHANGES OF I S O L A T E D G U I N E A PIG ATRIA. H. Seifart, S. Poplawski, M. Siess, D e p a r t m e n t of P h a r m a c o l o g y , U n i v e r s i t y of T u e b i n g e n , D-7400 Tuebingen, West Germany. The a u x o t o n i c c o n t r a c t i l e w o r k per beat (cwb) of e l e c t r i c a l l y d r i v e n left atria in Krebs H e n s e l e i t s o l u t i o n w i t h 15 mM glucose was m e a s u r e d under a e r o b i c and a n a e r o b i c c o n d i t i o n s b e t w e e n 30 and 150 beats per m i n u t e and t e m p e r a t u r e s of 25~ 30~ and 35~ respectively. Under acute anoxia (95% N2/5% CO 2) the time course to s t a n d s t i l l d e p e n d s on cwb, f r e q u e n c y and energy supply by a n a e r o b i c glycolysis. L o w e r i n g the f r e q u e n c y in an o x y g e n a t e d m e d i u m at 35~ from 90 b/min to 30 b/min, the cwb d e c r e a s e s from 100% to 20%; d u r i n g acute anoxia at 30 b / m i n this value is further r e d u c e d to 15% but can be e n h a n c e d by g - s t r o p h a n t h i n or n i c o t i n a m i d e to values
D E M O N S T R A T I O N OF H I S T A M I N E - S E N S I T I V E A D E N Y L ATE CYCLASE IN C A P I L L A R I E S OF G U I N E A PIG MYOCARDIUM. W. Schulze, A. W o l l e n b e r g e r . Centr. Inst. of Heart and Circul. Reg. Res., Acad. Sci. of the DDR, B e r l i n - B u c h , GDR. At p r e s e n t h i s t o c h e m i c a l and c y t o c h e m i c a l m e t h o d s are the sole means for d e m o n s t r a t i n g adenylate cyclase a c t i v i t y in the c a p i l l a r i e s of the coronary circulation. In our study sections of guinea pig v e n t r i c u l a r m u s c l e w e r e i n c u b a t e d in m e d i u m c o n t a i n i n g adenylyl i m i d o d i p h o s p h a t e as a fairly s p e c i f i c s u b s t r a t e of a d e n y l a t e cyclase and free lead ions at appr. 4x10 -5 M. E l e c t r o n dense reaction product, p r e s u m a b l y lead i m i d o d i p h o s p h a t e , was d e p o s i t e d in the m y o c a r d i a l cells at the s a r c o l e m m a and the T - t u b u l e s and in the c a p i l l a r i e s at the p l a s m a m e m b r a n e and p i n o c y t o t i c v e s i c l e s of the e n d o t h e l i a l cells. The r e a c t i o n in the c a p i l l a r i e s was m a r k e d l y e n h a n c e d by 10 -4 M h i s t a m i n e and this e n h a n c e m e n t was r e d u c e d by the H l - r e c e p t o r b l o c k e r m e p y r a m i n e (10 -5 M), but not by the H 2 - r e c e p t o r b l o c k e r b u r i m a m i d e (4x10 -4 M). The s t i m u l a t o r y effect of h i s t a m i n e on c y t o c h e m i c a l l y d e m o n s t r a b l e a d e n y l a t e cyclase in the e n d o t h e l i a l cells of the c a p i l l a r i e s may be an i n t e r m e d i a t e step in the a c t i o n of this amine on c a p i l l a r y p e r m e a b i l i t y in the heart.
80.
A N A E R O B I C C O N T R A C T I L E A C T I V I T Y AND M E T A B O L I C CHANGES OF I S O L A T E D G U I N E A PIG ATRIA. H. Seifart, S. Poplawski, M. Siess, D e p a r t m e n t of P h a r m a c o l o g y , U n i v e r s i t y of T u e b i n g e n , D-7400 Tuebingen, West Germany. The a u x o t o n i c c o n t r a c t i l e w o r k per beat (cwb) of e l e c t r i c a l l y d r i v e n left atria in Krebs H e n s e l e i t s o l u t i o n w i t h 15 mM glucose was m e a s u r e d under a e r o b i c and a n a e r o b i c c o n d i t i o n s b e t w e e n 30 and 150 beats per m i n u t e and t e m p e r a t u r e s of 25~ 30~ and 35~ respectively. Under acute anoxia (95% N2/5% CO 2) the time course to s t a n d s t i l l d e p e n d s on cwb, f r e q u e n c y and energy supply by a n a e r o b i c glycolysis. L o w e r i n g the f r e q u e n c y in an o x y g e n a t e d m e d i u m at 35~ from 90 b/min to 30 b/min, the cwb d e c r e a s e s from 100% to 20%; d u r i n g acute anoxia at 30 b / m i n this value is further r e d u c e d to 15% but can be e n h a n c e d by g - s t r o p h a n t h i n or n i c o t i n a m i d e to values