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Mediation of the positive chronotropic effect of CGP 12177 and cyanopindolol in the pithed rat by atypical β‐adrenoceptors, different from β 3 ‐adrenoceptors
Author(s) -
Malinowska Barbara,
Schlicker Eberhard
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15285.x
Subject(s) - chronotropic , fenoterol , medicine , endocrinology , agonist , antagonist , isoprenaline , heart rate , blood pressure , chemistry , receptor , stimulation , asthma
1 The influence of β 1 , β 2 , and β 3 ‐adrenoceptor agonists and of CGP 12177 and cyanopindolol on heart rate and diastolic blood pressure was studied in the pithed rat. 2 The β 1 ‐adrenoceptor agonist, prenalterol, increased heart rate and the β 2 ‐adrenoceptor agonist, fenoterol, caused a fall in blood pressure. The effect of prenalterol was antagonized by the β 1 ‐adrenoceptor antagonist, CGP 20712 0.1 μ m ol kg −1 and the action of fenoterol was attenuated by the β 2 ‐adrenoceptor antagonist, ICI 118551 0.1 μ m ol kg −1 . Both effects were markedly diminished by the non‐selective β‐adrenoceptor antagonist, bupranolol 0.1 μ m ol kg −1 . 3 The non‐selective β‐adrenoceptor agonist, isoprenaline, three β 3 ‐agonists as well as CGP 12177 and cyanopindolol elicited a positive chronotropic effect, exhibiting the following pED A60 values (negative log values of the doses increasing heart rate by 60 beats min −1 ): isoprenaline 10.4, CGP 12177 8.3, cyanopindolol 7.2, BRL 37344 6.9, ZD 2079 5.2 and CL 316243 <5. 4 CGP 20712 0.1 μ m ol kg −1 , given together with ICI 118551 0.1 μ m ol kg −1 , markedly attenuated the positive chronotropic effect of isoprenaline, BRL 37344, ZD 2079 and CL 316243 without affecting the increase in heart rate produced by CGP 12177 and cyanopindolol. 5 The positive chronotropic effect of CGP 12177 and cyanopindolol was attenuated by CGP 20712, 1 and 10 μ m ol kg −1 and bupranolol, 10 μ m ol kg −1 but was not affected by ICI 118551, 10 μ m ol kg −1 . The effect of CGP 12177 was also not changed by BRL 37344 1 μ m ol kg −1 , ZD 2079 10 μ m ol kg −1 , CL 316243 10 μ m ol kg −1 , the α 1 ‐adrenoceptor antagonist, prazosin 1 μ m ol kg −1 and the 5‐hydroxytryptamine 5‐HT 2A receptor antagonist, ketanserin 3 μ m ol kg −1 . 6 CGP 12177 0.002 μ m ol kg −1 and cyanopindolol 0.003 μ m ol kg −1 shifted to the right the dose‐response curve of prenalterol for its positive chronotropic effect. The ‐log values of the doses causing a twofold shift to the right were 9.6 and 9.5, respectively. 7 Isoprenaline 0.00001‐0.001 μ m ol kg −1 , BRL 37344 0.01‐1 μ m ol kg −1 and CGP 12177 0.1 μ m ol kg −1 caused a fall in diastolic blood pressure which was markedly attenuated by combined administration of CGP 20712 and ICI 118551, 0.1 μ m ol kg −1 each. 8 CGP 12177 0.01 and 0.1 μ m ol kg −1 and cyanopindolol 1 μ m ol kg −1 elicited an increase in diastolic blood pressure. CGP 20712, ICI 118551, bupranolol and, in the case of CGP 12177, also BRL 37344, ZD 2079, CL 316243, prazosin and ketanserin did not influence this effect. 9 In conclusion, the positive chronotropic effect of CGP 12177 and cyanopindolol is not mediated via β 1 ‐, β 2 ‐, β 3 ‐, α 1 ‐adrenoceptors or 5‐HT 2A receptors. This effect may involve atypical β‐adrenoceptors, similar or identical to those described by Kaumann (1989) in isolated heart preparations.