title: Canine intrinsic cardiac neurons involved in cardiac regulation possess NK1, NK2, and NK3 receptors.
abstract: To determine whether intrinsic cardiac neurons involved in cardiac regulation possess neurokinin (NK) receptor subtypes, we administered selective NK receptor agonists individually (100 microM; 0.1 ml) into the coronary arterial blood supply of right atrial intrinsic cardiac neurons of 18 anesthetized dogs. The selective NK1 receptor agonist [Sar9,Met(O2)11]-substance P depressed the spontaneous activity of right atrial neurons (26.7 +/- 6.7 to 13.0 +/- 4.0 impulses/min; P < 0.05) in 11 dogs and augmented such activity in the other 5 dogs (8.0 +/- 3.1 to 27.8 +/- 8.7 impulses/min; P < 0.05). Local administration of the selective NK2 receptor agonist [beta-Ala8]-NKA-(4-10) depressed right atrial neuronal activity (27.3 +/- 6.4 to 14.7 +/- 3.8 impulses/min; P < 0. 05), whereas the selective NK3 receptor agonist senktide augmented such activity (18.9 +/- 6.4 to 53.1 +/- 12.0 impulses/min; P < 0.05). Left ventricular chamber pressure fell when selective NK1 and NK2 receptor agonists were administered. Increases in heart rate and right ventricular intramyocardial systolic pressure occurred when the selective NK3 receptor agonist was studied. Administration of a selective NK1 or NK2 receptor antagonist altered neuronal activity, with no subsequent change in activity occurring after administration of its respective receptor agonist. Receptor autoradiography demonstrated tachykinin receptors associated with ventral right atrial intrinsic cardiac neurons. It is concluded that intrinsic cardiac neurons involved in cardiac regulation possess NK1, NK2, and NK3 receptors and that some intrinsic cardiac neurons receive tonic input via endogenously released NKs.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
authors.forename: G W
authors.initials: GW
authors.lastname: Thompson
authors.forename: D B
authors.initials: DB
authors.lastname: Hoover
authors.forename: J L
authors.initials: JL
authors.lastname: Ardell
authors.forename: J A
authors.initials: JA
authors.lastname: Armour
mesh_terms: D000818:Animals; D004285:Dogs; D006321:Heart / Q000294:innervation* / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000502:physiology*; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C054724:senktide; C062618:substance P, Sar(9)-Met(O2)(11)-; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; D015288:Neurokinin A