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Cycloheximide as an alpha1-adrenergic agonist and A β-antagonist in cultured rat heart cells
196mTmacTIoN
BETWEEN a-ADRENERGIC AND B-ADRENERGIC INOTROPIC EFFECTS OF NORADRENALINE IN RABBIT PAPILLARY MUSCLES. H. Aass, T. Skomedal & J.-B. Osnes, Department of Pharmaof Oslo, P.O.Box 1057, Blinder”, Oslo 3, Norway. cology I University The time courses of pure i\-adrenergic, pure fi-adrenergic and combined ‘i- and I--adrenergic inotropic effects of 6.5~10~~ mol/l “oradrenallne (NA) were studled in ~sometrically contracting rabbit papillary muscles by applying appropriate blockers. Th? pure rc-adrenergic inotropic effect (NA 1” the presence of 5x10-” mol/l propranolol) developed relatively slowly after a lag phase of 3314 set (“=5). Time to half response was 100’3 sec. There was a slight but slgnlflcant prolonqation of the tlm? to peak tension (4+1 msec). The pure P-adrenergic rrspo~lse to NA (in the prfsencc of 1Cle7 mol/l prazosin) developed relatively rapidly with a la3 phase of 7.4'0.2 set and time to half response 19+2 set ln=i). There was a signlflcant shortening of time to r,eak tension (37!4 msec). In the absence of blockers the all over response to NA developed relatively rapidly with a lag phase of 5.H’O.i set and time to half rrspo”se 49+7 sue (“=6). The time course consIsted of a rapld initial increase, followed hy a short reductlon or a plateau before the final increase. Ths time course was thus intermedlxry to that of pure ‘Y- and pure F-adrenerglc stimulation. ‘The qualitative changes of t!lccontraction-relaxation cycle after stimulatlnn by NA &lone was rather slmllar to the pure :2-adrenergic effect, with a shortenlny nf the time to peak tenslo” of 33’4 mscc. The time course, however, revealed that the lnotroplc response to NA was the rcsultant of a combined II- and [?-adrenoceptor stlimllatio” I” rahbjlt )>apll l/ir\: mliscles.
197CYCLOHEXIMIDE AS An' ALPHAl-ADREFERGIC AGONIST A?D A B-AKTAGONIST IN CULTURED RAT HEART CELLS. A. Wollenberger and G. Wallukat. Ctr. Inst. of Heart & Circul. Res., Berlin-Buch, German Democratic Republic. Cycloheximide at concentrations between 0.01 and 1 mM increased the rate of beating of rocker-cultured neonatal rat myocardisl cells through activation of alphalradreygceptors. At concentrations between between 1 and 1000 nM, at which C Cjleucine incorporation into the cultured cells was not or not greatly affected, the antibiotic inhibited surmountably the positive chronotropic action of the rather nonselective B-adrenergic agonist isoprenaline, A potent positive chron.. otropic action of the I32-selective adrenergic agonist clenbuterol was Neither did cycloheximide (IO and 1000 not opposed by cycloheximide. nM) influence the acceleration of beating by phenylephrine, dibutyryl cyclic AMP, and elevation of the extracellular $~~~7i~d~~r~~~~~~t~Or~m Displacement of the nonselective O-antagonist c its specific binding sites on the cultured heart cells by cycloheximwith about 30 per cent of the displacement Occurring ide was diphasic, below 10 nM cycloheximide (IC 0 = 2 nM) and the remaining 70 per cent the action Of 106~ above 10,000 nM. Experiments 2 esigned to delineate concentrations of cycloheximide on R-receptors are current&in mress. 198ENHANCEDRESPONSIVENESS 'r0
NORADRENALINE OF CARDIAC PUKKIN.IF: FIHERS EXPOSED TO ANoXI(‘ GLUCOSE-FREE SOLUTION: A ROLE FOR ALPHA-ADRENOCEPTORS? Mugelli,A., Amerini, S., Piazzesi, G., Giotti, A. Center for Electrophysiological Investigations in Phdrmacolilgy, Department of Pharmacoloyy, University of Florence, Florence, Italy. ‘The induction and/or acceleration of spontaneous activity caused by catecholamines in Purkinje fibers is attributed to a beta-adrenergic effect, while cardiac alphaadrenuceptors do not appear tobedirectly involved in controlling the procrss of diii,cts r in the absence vf bet:ibluckade, was unaffected by praaosin (10 -7 N), was sly slightly reduced by phentulJmine (3x10-7 M) and was cvnsistrntly slowed ur blocked hy y(lhimbinf (10m7 M). This wurk was supported bv C?;R grant CT 82.02041.0&.
BETWEEN a-ADRENERGIC AND B-ADRENERGIC INOTROPIC EFFECTS OF NORADRENALINE IN RABBIT PAPILLARY MUSCLES. H. Aass, T. Skomedal & J.-B. Osnes, Department of Pharmaof Oslo, P.O.Box 1057, Blinder”, Oslo 3, Norway. cology I University The time courses of pure i\-adrenergic, pure fi-adrenergic and combined ‘i- and I--adrenergic inotropic effects of 6.5~10~~ mol/l “oradrenallne (NA) were studled in ~sometrically contracting rabbit papillary muscles by applying appropriate blockers. Th? pure rc-adrenergic inotropic effect (NA 1” the presence of 5x10-” mol/l propranolol) developed relatively slowly after a lag phase of 3314 set (“=5). Time to half response was 100’3 sec. There was a slight but slgnlflcant prolonqation of the tlm? to peak tension (4+1 msec). The pure P-adrenergic rrspo~lse to NA (in the prfsencc of 1Cle7 mol/l prazosin) developed relatively rapidly with a la3 phase of 7.4'0.2 set and time to half response 19+2 set ln=i). There was a signlflcant shortening of time to r,eak tension (37!4 msec). In the absence of blockers the all over response to NA developed relatively rapidly with a lag phase of 5.H’O.i set and time to half rrspo”se 49+7 sue (“=6). The time course consIsted of a rapld initial increase, followed hy a short reductlon or a plateau before the final increase. Ths time course was thus intermedlxry to that of pure ‘Y- and pure F-adrenerglc stimulation. ‘The qualitative changes of t!lccontraction-relaxation cycle after stimulatlnn by NA &lone was rather slmllar to the pure :2-adrenergic effect, with a shortenlny nf the time to peak tenslo” of 33’4 mscc. The time course, however, revealed that the lnotroplc response to NA was the rcsultant of a combined II- and [?-adrenoceptor stlimllatio” I” rahbjlt )>apll l/ir\: mliscles.
197CYCLOHEXIMIDE AS An' ALPHAl-ADREFERGIC AGONIST A?D A B-AKTAGONIST IN CULTURED RAT HEART CELLS. A. Wollenberger and G. Wallukat. Ctr. Inst. of Heart & Circul. Res., Berlin-Buch, German Democratic Republic. Cycloheximide at concentrations between 0.01 and 1 mM increased the rate of beating of rocker-cultured neonatal rat myocardisl cells through activation of alphalradreygceptors. At concentrations between between 1 and 1000 nM, at which C Cjleucine incorporation into the cultured cells was not or not greatly affected, the antibiotic inhibited surmountably the positive chronotropic action of the rather nonselective B-adrenergic agonist isoprenaline, A potent positive chron.. otropic action of the I32-selective adrenergic agonist clenbuterol was Neither did cycloheximide (IO and 1000 not opposed by cycloheximide. nM) influence the acceleration of beating by phenylephrine, dibutyryl cyclic AMP, and elevation of the extracellular $~~~7i~d~~r~~~~~~t~Or~m Displacement of the nonselective O-antagonist c its specific binding sites on the cultured heart cells by cycloheximwith about 30 per cent of the displacement Occurring ide was diphasic, below 10 nM cycloheximide (IC 0 = 2 nM) and the remaining 70 per cent the action Of 106~ above 10,000 nM. Experiments 2 esigned to delineate concentrations of cycloheximide on R-receptors are current&in mress. 198ENHANCEDRESPONSIVENESS 'r0
NORADRENALINE OF CARDIAC PUKKIN.IF: FIHERS EXPOSED TO ANoXI(‘ GLUCOSE-FREE SOLUTION: A ROLE FOR ALPHA-ADRENOCEPTORS? Mugelli,A., Amerini, S., Piazzesi, G., Giotti, A. Center for Electrophysiological Investigations in Phdrmacolilgy, Department of Pharmacoloyy, University of Florence, Florence, Italy. ‘The induction and/or acceleration of spontaneous activity caused by catecholamines in Purkinje fibers is attributed to a beta-adrenergic effect, while cardiac alphaadrenuceptors do not appear tobedirectly involved in controlling the procrss of di