HISTAMINE INHIBITS CARDIAC SYMPATHETIC NEUROTRANSMISSION BY INTERACTING WITH H(3)-SUBTYPE OF HISTAMINE-RECEPTORS

The present study was designed to investigate the modulation of histam ine on cardiac sympathetice neurotransmission. In the presence of chlo rpheniramine (1 mumol L-1), ranitidine (10 mumol L-1), desmethylimipra mine (0.1 mumol L-1) and normetanephrine (1 mumol L-1), histamine (1 n mol L-1-100 mumol L-1) concentration-dependently depressed the sympath etic contractile responses induced by trains of field pulses in isolat ed guinea pig atria stimulated at 4 Hz. This inhibitory effect was ant agonised by H-3-antagonist burimamide and thioperamide in a concentrat ion-dependent manner with a IC50 values of 0.23 mumol L-1, 0.11 mumol L-1 respectively. At concentrations of 1 mumol L-1 and 10 mumol L-1, h istamine produced a downward shift of the stimulus-inotropic response curve. Blockade of alpha2- or beta2-adrenoceptors failed to prevent th e inhibitory effect of histamine. The positive inotropic response indu ced by exogenously-applied norepinephrine was not inhibited but potent iated by histamine. Our results indicate that inhibition of cardiac sy mpathetic neurotransmission by histamine is mediated by histamine H-3- receptor which might exist on sympathetic nerve terminals in guinea pi g atria.