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POSSIBLE ROLE OF A β‐ADRENOCEPTOR IN THE REGULATION OF NORADRENALINE RELEASE BY NERVE STIMULATION THROUGH A POSITIVE FEED‐BACK MECHANISM
Author(s) -
ADLERGRASCHINSKY EDDA,
LANGER S.Z.
Publication year - 1975
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.1476-5381.1975.tb07328.x
Subject(s) - phentolamine , propranolol , isoprenaline , stimulation , chronotropic , endocrinology , medicine , chemistry , guinea pig , heart rate , biology , blood pressure
1 The effects of isoprenaline, propranolol and phentolamine, were studied on tritiated noradrenaline overflow elicited by postganglionic nerve stimulation in guinea‐pig isolated atria. 2 Isoprenaline (1.2 × 10 −8 ) increased while propranolol (1.0 × 10‐ 7 M) reduced the overflow of tritiated noradrenaline evoked by nerve stimulation. These effects were less than those of phentolamine (3.1 × 10‐ 6 M), which increased by approximately three‐fold the overflow of [ 3 H] ‐noradrenaline elicited by nerve stimulation. 3 Neuronal accumulation of tritiated noradrenaline in guinea‐pig atria was not affected by isoprenaline, propranolol or phentolamine at the concentrations employed in this study. 4 Isoprenaline (1.2 × 10‐ 8 M) induced a positive chronotropic effect of about 80% of the maximum. On the other hand, propranolol produced a shift to the right in the frequency‐response curve to nerve stimulation and in the concentration‐response curve to exogenous noradrenaline in guinea‐pig atria. 5 In the isolated nictitating membrane of the cat, the frequency‐response curve to nerve stimulation was not modified by propranolol, while in the presence of 3.9 × 10 −6 m of N ,‐2‐(2,6‐dimethylphenoxy)propyl‐ N,N,N ‐trimethylammonium (β‐methyl‐TM 10) there was a shift to the right and a depression of slope. Neither propranolol nor β‐methyl‐TM 10 affected responses to exogenous noradrenaline. 6 The effects of isoprenaline and of propranolol on transmitter release are compatible with the view that in addition to the presynaptic negative feed‐back mechanism for noradrenaline release by nerve stimulation mediated via α‐adrenoceptors a positive feed‐back mechanism exists in adrenergic nerve endings which is triggered through the activation of presynaptic β‐adrenoceptors.