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Heterogeneity of prejunctional NPY receptor‐mediated inhibition of cardiac neurotransmission
Author(s) -
Serone Adrian P,
Wright Christine E,
Angus James A
Publication year - 1999
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 - 10.1038/sj.bjp.0702519
Subject(s) - endocrinology , medicine , neuropeptide y receptor , agonist , bethanechol , chemistry , neurotransmission , chronotropic , receptor , receptor antagonist , antagonist , biology , neuropeptide , muscarinic acetylcholine receptor , heart rate , blood pressure
Neuropeptide Y (NPY) has been proposed as the candidate inhibitory peptide mediating interactions between sympathetic and vagal neurotransmission in several species, including man. Here, we have defined the NPY receptors involved in modulation of cardiac autonomic neurotransmission using receptor‐selective agonists and antagonists in the rabbit and guinea‐pig isolated right atria. In isolated atrial preparations, sympathetically‐mediated tachycardia (ST; with atropine 1 μ M ) or vagally‐mediated bradycardia (VB; with propranolol 0.1–1 μ M ) in response to electrical field stimulation (EFS, 1–4 pulses) were tested 0–30 min after incubation with single concentrations of vehicle, NPY (0.01–10 μ M ), the Y 2 receptor agonist N‐Acetyl‐[Leu 28,31 ]NPY(24–36) (termed N ‐A[L]NPY(24–36)) or the Y 1 receptor agonist [Leu 31 ,Pro 34 ]NPY (LP). The effect of NPY on the concentration‐chronotropic response curves to isoprenaline and bethanechol were also assessed. Guinea‐pig atria: NPY and N ‐A[L]NPY(24–36) caused concentration‐dependent inhibition of VB and ST to EFS. Both peptides caused maximal inhibition of VB and ST within 10 min incubation and this remained constant. LP caused a concentration‐dependent, transient inhibition of ST which was antagonized by the Y 1 ‐receptor antagonist GR231118 (0.3 μ M ), with apparent competitive kinetics. Rabbit atria: NPY (1 or 10 μ M ) had no effect on VB at any time point, but both NPY and LP caused a transient (∼10 min) inhibition of sympathetic tachycardia. This inhibition could be prevented by 0.3 μ M GR231118. N ‐A[L]NPY(24–36) had no effect on ST. NPY had no effect on the response to β‐adrenoceptor stimulation by isoprenaline nor muscarinic‐receptor stimulation by bethanechol in either species. Thus, in the guinea‐pig, NPY causes a stable inhibition of both VB and ST to EFS via Y 2 receptors and transient inhibition of ST via Y 1 receptors. In contrast in the rabbit, NPY has no effect on the cardiac vagus and prejunctional inhibition of ST is transient and mediated by a Y 1 ‐like receptor (rather than Y 2 ). Therefore it would be surprising if NPY plays a functional role in modulation of cardiac neurotransmission in the rabbit.British Journal of Pharmacology (1999) 127 , 99–108; doi: 10.1038/sj.bjp.0702519