Presynaptic beta-adrenoceptors in rat atria: evidence for the presence of stereoselective beta 1-adrenoceptors.
1. Presynaptic beta-adrenoceptor activity was studied in rat isolated atria, previously loaded with [3H]-noradrenaline. The stimulation-induced release of 3H transmitter was measured in the presence of cocaine, and adrenaline was used as a facilitatory beta-adrenoceptor agonist. 2. Adrenaline (0.1 and 2 nM) increased, by about 50%, the evoked efflux of tritium. With phenoxybenzamine present, the same activity was shown with 10 nM adrenaline. 3. The beta 2-selective adrenoceptor blocking drugs: IPS 339 and ICI 118 551 caused a concentration-dependent decrease in the activity of adrenaline. Cardioselective beta-blocking drugs: acebutolol, beta-xolol, nebivolol and its isomers (R 67 138 and R 67 145) also reduced dose-dependently the agonistic action of adrenaline. The order of potency for nebivolol and its isomers was R 67 138 greater than nebivolol greater than R 67 145. The activity of pindolol was not concentration-dependent. The inhibitory effect of acebutolol was also observed in the presence of blockade of alpha-adrenoceptors. 4. The postsynaptic beta-adrenoceptor blocking activity of nebivolol and its isomers was studied in pithed rats. They reduced isoprenaline-induced tachycardia without altering hypotensive responses. The order of potency was: R 67 138 greater than nebivolol greater than R 67 145. 5. It is concluded that in rat isolated atria, presynaptic beta 2- and beta 1-adrenoceptors coexist and that facilitatory beta 1-adrenoceptors are stereospecific.
Heimburger
M
M
Laboratoire de Pharmacologie, U.A.-C.N.R.S. 594, Faculté de Pharmacie, Université Paris-Sud, France.
Montero
M J
MJ
Fougeres
V
V
Beslot
F
F
Davy
M
M
Midol-Monnet
M
M
Cohen
Y
Y
D000070:Acebutolol / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003655:Decerebrate State; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D010643:Phenoxybenzamine; D000070:Acebutolol; D009638:Norepinephrine; D004837:Epinephrine