Histamine H3-receptors inhibit sympathetic neurotransmission in guinea pig myocardium.
The histamine H3 agonist, (R)-alpha-methylhistamine (alpha-MeHA, 10(-10) to 10(-5) M), caused a concentration-dependent inhibition of the sympathetic contractile response to electrical field stimulation of guinea pig isolated atria, but alpha-MeHA did not alter the basal tension or the contraction induced by exogenously applied norepinephrine. Blockade of H1 and H2 histamine receptors, and alpha- and beta-adrenoceptors failed to prevent the inhibitory effect of alpha-MeHA, whereas the specific H3 receptor antagonist, thioperamide, concentration dependently reversed the inhibitory effect of alpha-MeHA. At the concentration of 10(-7) M, which was effective for antagonizing the action of alpha-MeHA, thioperamide did not modify the sympathetic responses facilitated by the beta 2-adrenoceptor agonist, clenbuterol, or attenuated by the alpha 2-adrenoceptor agonist, clonidine. Our results suggest that H3 receptors exist on the cardiac sympathetic terminals, which may modulate adrenergic neurotransmission in guinea pig myocardium.
Luo
X X
XX
Department of Pharmacology, Fourth Military Medical University, Xian, China.
Tan
Y H
YH
Sheng
B H
BH
D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D006325:Heart Atria; D066298:In Vitro Techniques; D008761:Methylhistamines / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology*; D018100:Receptors, Histamine H3; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D008761:Methylhistamines; D010880:Piperidines; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D002744:Chlorpheniramine; C069357:alpha-methylhistamine; D011899:Ranitidine; D011433:Propranolol; C052075:thioperamide; D003000:Clonidine; D009638:Norepinephrine; D002976:Clenbuterol; D010646:Phentolamine