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Myosin adenosine triphosphatase activities in hypertrophied pig heart
J Mol Cell Cardiol 18 (Supplement 3) (1986) PHARMACOLOGICAL DIFFERENCES BETWEEN ATRIAL AND SMOOIH MUSCLE MUSCARINIC RECEPIORS. R.M. E g l e n , M. H u f f , W. Montgomery, A.N. S t r o s b e r g , and R . L . W h i t i n g . Department o f P h a r m a c o l o g y , S y n t e x Research, 3 4 0 1 H i l l v i e w Avenue, Palo A l t o , CA 94304 USA. M u s c a r i n i c r e c e p t o r s a r e c o n s i d e r e d t o form m u l t i p l e s u b t y p e s and a r e c u r r e n t l y classified according to their affinities towards the antagonist pirenzepine. The aim o f t h e p r e s e n t s t u d y was t o assess t h e a f f i n i t i e s of muscarinic antagonists at i l e a l and a t r i a l muscarinic receptors in vitro. Affinities (pA 2 v a l u e s ) were e s t i m a t e d u s i n g c a r b a c h o l as t h e a g o n i s t a f t e r t h e method o f A r u n l a k s h a n a and Schild (1959). D e t a i l s o f t h e p r o t o c o l a r e d e s c r i b e d by Clague e t a l . , ( 1 9 8 5 ) . The a f f i n i t i e s o f p i r e n z e p i n e (PZ) and a t r o p i n e (A) were s i m i l a r a t b o t h r e c e p t o r s ( i l e u m PZ=6.8, A = 9 . 0 ; a t r i a PZ=6.7, A = 8 . 9 ) . In contrast, sila-procyclidine (S) and 4-OAHP ( 0 ) were more s e l e c t i v e f o r t h e i l e a l r e c e p t o r s ( i l e u m S = 8 . 9 , D=8.9;
a t r i a S=7.5, D=7.8). ConversIy, AF-DX 116 (A) and gallamine (G) were more selective for the a t r i a l receptors (ileum A=S.8, G=4.8; a t r i a A=6.4, G=5.8). In summary, muscarinic receptors present in the a t r i a appear to d i f f e r pharmacologically from those in the ileum. Differences in these receptors may lead to development of novel selective therapeutic muscarinic agents. Arunlakshana, A.D. and Schild, H.O. (1959), Br. J. Pharmac. 14 48-58. Clague, R.U., et a t . , (1985), Br. J. Pharmac. 86 163-170.
MYOSIN ADENOSINE TRIPHOSPHATASE ACTIVITIES IN HYPERTROPHIED PIG HEART. V. Ellmban, K.S. Dhalla, P.~. $ingal, V. Panagla, N.S. Dhalla. Department of PbysloloKy, U~Iverslty of Manltoba, Canada R3E 0W3. Although changes in myosin ATPase activities have been identified in oardlao hypertrophy, very little information regarding the time-course of these alterations is available in the llterature. A non-faillng hypertrophy of the left ventricle was induced in pigs by supravalvular banding of the aorta for q, 8 and 12 weeks and ATPase activities were measured to assess their altered contractile functions. The presence of hypertrophy in these animals was confirmed by an inoEease in the left vantrioular wall thickness. ~ slEnlfloant increase in myosin Ca z+ ATPase activity was seen at q weeks of hypertrohpy, but at 8 end 12 weeks this activity was markedly decreased in oomparlson to the sham control values. Silailarly, the actin-aotlvated myosin ATPase activity was increased at q weeks and decreased at 8 end 12 weeks of hypertrophy. Slnoe the K +- or NH~+-EDTA stimulated ATPase activities in myosin were not altered at any ~tage of hypertrophy~ it appears that changes in myosin may be o o o u r r i n g at the Ca ~+ binding sites. The observed Increase in myosin ATPase aotlvlty at initial stakes of hypertrophy may be adaptive in nature and may account for the hyperfunotlon of the myooardlum. The later depression in myosin ATPase activity may be associated with the development of pathological hypertrophy. (Supported by the Medical Research Council of Canada).
ALPHA- ANO BETA-AORENOCEPfOR HEOIATEO HYOCAROIAL POTASSIUM UPTAKE. B. E l l i n g s e n , B.A. Vengen and A. I l e b e k k . Institute for E x p e r i m e n t a l M e d i c a l Research, U n i v e r s i t y o f Oslo, Norway. Changes i n m y o c a r d i a l p o t a s s i u m (K*) b a l a n c e d u r i n g i n t r a c o r o n a r y (ic) infusion of isoproterenol (]SO) and p h e n y l e p h r i n e (PHE), were d e t e r m i n e d i n 10 a n e s t h e t i z e d open c h e s t piglets (22-35 kg). K+ c o n c e n t r a t i o n s were c o n t i n u o u s l y r e c o r d e d by PVC-valinomycin mini-electrodes in arterial blood in the left atrium (a) and i n m y o c a r d i a l venous b l o o d i n a shunt f r o m t h e c o r o n a r y s i n u s (cs) t o t h e r i g h t a t r i u m . Accumulated myocardial K+ u p t a k e from s t a r t o f an i c drug infusion to a new steady state (3.5-7.5 min), was c a l c u l a t e d from o n - l i n e d a t a s a m p l i n g s . Continuous ic I$O i n f u s i o n , 2 . 5 n m o l l m i n , caused a peak a - c s K d i f f e r e n c e o f 0.37 ( 0 . 2 3 - 0 . 5 3 ) mH (median and 95Z c o n f . i n t e r v a l ) at 2.5 (2.0-&.0) min and an accumulated K+ u p t a k e o f 139 ( 6 3 - 2 1 5 ) p m o l / 1 0 0 g . After intravenous (iv) infusion of 2.7 ( 2 . 2 - 3 . 1 ) ~ m o l / k g p r o p r a n o l o l , ISO d i d n o t change K+ b a l a n c e s i g n i f i c a n t l y ; b u t i c PHE tOO n m o l / m i n , w h i c h e x e r t e d maximal change i n K* b a l a n c e , induced a peak a - c s d i f f e r e n c e o f 0.1E ( 0 . 1 3 - 0 . 2 1 ) mM a t 1.T5 ( 1 . 5 - 2 . 0 ) min, and an accumulated K+ u p t a k e o f 30 ( 2 0 - 4 1 ) p m o l / t 0 0 g . A f t e r i v p r a z o s i n , 2T0 ( 2 4 0 - 3 0 0 ) n m o l / k g , PHE d i d n o t change K+ b a l a n c e s i g n i f i c a n t l y . Thus, b o t h ~- and ~ - s t i m u l a t i o n i n d u c e a m y o c a r d i a l K+ u p t a k e , t h e l a t t e r more m a r k e d l y ( d i f f e r e n c e p< 0 . 0 0 t ) .
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a t r i a S=7.5, D=7.8). ConversIy, AF-DX 116 (A) and gallamine (G) were more selective for the a t r i a l receptors (ileum A=S.8, G=4.8; a t r i a A=6.4, G=5.8). In summary, muscarinic receptors present in the a t r i a appear to d i f f e r pharmacologically from those in the ileum. Differences in these receptors may lead to development of novel selective therapeutic muscarinic agents. Arunlakshana, A.D. and Schild, H.O. (1959), Br. J. Pharmac. 14 48-58. Clague, R.U., et a t . , (1985), Br. J. Pharmac. 86 163-170.
MYOSIN ADENOSINE TRIPHOSPHATASE ACTIVITIES IN HYPERTROPHIED PIG HEART. V. Ellmban, K.S. Dhalla, P.~. $ingal, V. Panagla, N.S. Dhalla. Department of PbysloloKy, U~Iverslty of Manltoba, Canada R3E 0W3. Although changes in myosin ATPase activities have been identified in oardlao hypertrophy, very little information regarding the time-course of these alterations is available in the llterature. A non-faillng hypertrophy of the left ventricle was induced in pigs by supravalvular banding of the aorta for q, 8 and 12 weeks and ATPase activities were measured to assess their altered contractile functions. The presence of hypertrophy in these animals was confirmed by an inoEease in the left vantrioular wall thickness. ~ slEnlfloant increase in myosin Ca z+ ATPase activity was seen at q weeks of hypertrohpy, but at 8 end 12 weeks this activity was markedly decreased in oomparlson to the sham control values. Silailarly, the actin-aotlvated myosin ATPase activity was increased at q weeks and decreased at 8 end 12 weeks of hypertrophy. Slnoe the K +- or NH~+-EDTA stimulated ATPase activities in myosin were not altered at any ~tage of hypertrophy~ it appears that changes in myosin may be o o o u r r i n g at the Ca ~+ binding sites. The observed Increase in myosin ATPase aotlvlty at initial stakes of hypertrophy may be adaptive in nature and may account for the hyperfunotlon of the myooardlum. The later depression in myosin ATPase activity may be associated with the development of pathological hypertrophy. (Supported by the Medical Research Council of Canada).
ALPHA- ANO BETA-AORENOCEPfOR HEOIATEO HYOCAROIAL POTASSIUM UPTAKE. B. E l l i n g s e n , B.A. Vengen and A. I l e b e k k . Institute for E x p e r i m e n t a l M e d i c a l Research, U n i v e r s i t y o f Oslo, Norway. Changes i n m y o c a r d i a l p o t a s s i u m (K*) b a l a n c e d u r i n g i n t r a c o r o n a r y (ic) infusion of isoproterenol (]SO) and p h e n y l e p h r i n e (PHE), were d e t e r m i n e d i n 10 a n e s t h e t i z e d open c h e s t piglets (22-35 kg). K+ c o n c e n t r a t i o n s were c o n t i n u o u s l y r e c o r d e d by PVC-valinomycin mini-electrodes in arterial blood in the left atrium (a) and i n m y o c a r d i a l venous b l o o d i n a shunt f r o m t h e c o r o n a r y s i n u s (cs) t o t h e r i g h t a t r i u m . Accumulated myocardial K+ u p t a k e from s t a r t o f an i c drug infusion to a new steady state (3.5-7.5 min), was c a l c u l a t e d from o n - l i n e d a t a s a m p l i n g s . Continuous ic I$O i n f u s i o n , 2 . 5 n m o l l m i n , caused a peak a - c s K d i f f e r e n c e o f 0.37 ( 0 . 2 3 - 0 . 5 3 ) mH (median and 95Z c o n f . i n t e r v a l ) at 2.5 (2.0-&.0) min and an accumulated K+ u p t a k e o f 139 ( 6 3 - 2 1 5 ) p m o l / 1 0 0 g . After intravenous (iv) infusion of 2.7 ( 2 . 2 - 3 . 1 ) ~ m o l / k g p r o p r a n o l o l , ISO d i d n o t change K+ b a l a n c e s i g n i f i c a n t l y ; b u t i c PHE tOO n m o l / m i n , w h i c h e x e r t e d maximal change i n K* b a l a n c e , induced a peak a - c s d i f f e r e n c e o f 0.1E ( 0 . 1 3 - 0 . 2 1 ) mM a t 1.T5 ( 1 . 5 - 2 . 0 ) min, and an accumulated K+ u p t a k e o f 30 ( 2 0 - 4 1 ) p m o l / t 0 0 g . A f t e r i v p r a z o s i n , 2T0 ( 2 4 0 - 3 0 0 ) n m o l / k g , PHE d i d n o t change K+ b a l a n c e s i g n i f i c a n t l y . Thus, b o t h ~- and ~ - s t i m u l a t i o n i n d u c e a m y o c a r d i a l K+ u p t a k e , t h e l a t t e r more m a r k e d l y ( d i f f e r e n c e p< 0 . 0 0 t ) .
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