Age-related subsensitivity of cerebellar Purkinje neurons to locally applied beta 1-selective adrenergic agonist. 1990

K D Parfitt, and P Bickford-Wimer
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.

Previous electrophysiological studies in aged rats have revealed a number of deficits in noradrenergic neurotransmission in the central nervous system. Such deficits include subsensitivity to the depressant effects of norepinephrine on cerebellar Purkinje neurons, which has been attributed specifically to altered beta adrenergic receptor-mediated processes. The objective of this study was to determine which beta adrenergic receptor subtype, beta 1 or beta 2, is responsible for this age-related subsensitivity. The effects of beta 1 and beta 2 agonists on spontaneous activity of Purkinje neurons was first examined in young rats and the selectivity of these agents was validated using selective beta 1 and beta 2 antagonists. The effects of the selective beta 1 and beta 2 agonists were then compared in young (3-month-old) and aged (18- and 26-month-old) Fischer 344 rats. These agents were applied to Purkinje neurons by pressure microejection from multibarreled micropipettes and the change in neuronal action potential discharge rate was recorded. Both dobutamine, a beta 1-selective agonist, and zinterol, a beta 2-selective agonist, induced dose-dependent inhibitions of Purkinje cell firing rate. Dobutamine-induced inhibitions were blocked by the selective beta 1 antagonist, ICI 89406 and not by the beta 2-selective antagonist, ICI 118551; conversely, zinterol-induced inhibitions were not blocked by ICI 89406 but were blocked by the presence of ICI 118551. Purkinje neurons of both groups of aged rats were significantly less sensitive to locally applied dobutamine than Purkinje cells of young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297 Male Males
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
D011689 Purkinje Cells The output neurons of the cerebellar cortex. Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002525 Cerebellar Cortex The superficial GRAY MATTER of the CEREBELLUM. It consists of two main layers, the stratum moleculare and the stratum granulosum. Cortex Cerebelli,Cerebelli, Cortex,Cerebellus, Cortex,Cortex Cerebellus,Cortex, Cerebellar
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D004280 Dobutamine A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY. Dobucor,Dobuject,Dobutamin Fresenius,Dobutamin Hexal,Dobutamin Solvay,Dobutamin-ratiopharm,Dobutamina Inibsa,Dobutamina Rovi,Dobutamine (+)-Isomer,Dobutamine Hydrobromide,Dobutamine Hydrochloride,Dobutamine Lactobionate,Dobutamine Phosphate (1:1) Salt, (-)-Isomer,Dobutamine Tartrate,Dobutamine Tartrate (1:1), (R-(R*,R*))-Isomer,Dobutamine Tartrate (1:1), (S-(R*,R*))-Isomer,Dobutamine, (-)-Isomer,Dobutamine, Phosphate (1:1) Salt (+)-Isomer,Dobutrex,Lilly 81929,Oxiken,Posiject,Dobutamin ratiopharm,Hydrobromide, Dobutamine,Hydrochloride, Dobutamine,Lactobionate, Dobutamine,Tartrate, Dobutamine
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D004983 Ethanolamines AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives. Aminoethanols

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