title: Enhancement by yohimbine of nicotine- and dimethylphenylpiperadinium-induced release of norepinephrine from cardiac sympathetic nerves of the dog: interaction of presynaptic alpha and nicotinic receptors.
abstract: The effect of yohimbine on nicotine- and dimethylphenylpiperadinium (DMPP)-induced release of norepinephrine (NE) from sympathetic cardiac nerves of the dog was examined in order to elucidate the interaction of presynaptic alpha and nicotinic receptors. Intracoronary infusion of nicotine (300 or 500 micrograms/min) or DMPP (100 or 300 micrograms/min) into the left circumflex artery increased coronary sinus output of NE (NE output), left ventricular dp/dt maximum (LV dp/dt max) and coronary sinus blood flow. The nicotine-induced increases in NE output, LV dp/dt max and coronary sinus blood flow were enhanced by simultaneous yohimbine infusion in doses of 10 and 30 micrograms/min into the same artery, and were attenuated by the drug in a dose of 100 micrograms/min. The DMPP-induced increases were enhanced by 10 micrograms/min of yohimbine infusion, but the enhancement was decreased by 30 and 100 micrograms/min. Yohimbine did not modify increases in NE output, LV dp/dt max and coronary sinus blood flow induced by intracoronary infusion of tyramine (100 micrograms/min). We have reported previously that yohimbine in the dose range used enhanced cardiac sympathetic nerve stimulation-induced increases in these parameters in a dose-dependent manner in the same preparation. The enhancement by yohimbine of nicotinic receptor-mediated NE release would be due to the blockade of presynaptic alpha-2 adrenoceptors. Therefore, it is suggested that presynaptic alpha-2 adrenoceptor-mediated feedback control operates on the process of NE release induced by nicotinic receptor activation as well as nerve stimulation. Although the mechanism of loss of the enhancement of the nicotinic effect by the large dose of yohimbine is not known, the possible mechanisms are discussed.
authors.affiliation: Department of Pharmacology, Tohoku University, Sendai, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kanda
authors.forename: H
authors.initials: H
authors.lastname: Koyanagawa
authors.forename: R
authors.initials: R
authors.lastname: Yorikane
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Satoh
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D011978:Receptors, Nicotinic; D015016:Yohimbine; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D009638:Norepinephrine; D014439:Tyramine