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. 1987

A Kanda, and H Koyanagawa, and R Yorikane, and T Kimura, and S Satoh
Department of Pharmacology, Tohoku University, Sendai, Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009538 Nicotine Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. Nicotine Bitartrate,Nicotine Tartrate
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011942 Receptors, Adrenergic, alpha One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation. Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D011978 Receptors, Nicotinic One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors. Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D003326 Coronary Circulation The circulation of blood through the CORONARY VESSELS of the HEART. Circulation, Coronary
D004246 Dimethylphenylpiperazinium Iodide A selective nicotinic cholinergic agonist used as a research tool. DMPP activates nicotinic receptors in autonomic ganglia but has little effect at the neuromuscular junction. DMPP,1,1-Dimethyl-4-phenylpiperazine Iodide,Dimethylphenylpiperazinium,1,1 Dimethyl 4 phenylpiperazine Iodide,Iodide, 1,1-Dimethyl-4-phenylpiperazine,Iodide, Dimethylphenylpiperazinium
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females

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