Effect of flow-stop on noradrenaline release from normal spleens and spleens treated with cocaine, phentolamine or phenoxybenzamine. 1971

S M Kirpekar, and M Puig

1. Cat spleens were perfused with Krebs-bicarbonate solution, using a constant-flow pump at a rate of about 7 ml/min at 33-35 degrees C. Noradrenaline (NA) overflow by nerve stimulation at 10 Hz for 20 s was determined with or without flow-stop before and after treatment with cocaine, phentolamine or phenoxybenzamine. In order to determine the effect of flow-stop on overflow, the arterial and the venous flows were occluded by clamping the inflow and outflow tubes during the period of stimulation plus 30, 60 or 120 seconds.2. Without flow-stop, NA output was 0.93+/-0.25 ng/stimulus, which was significantly increased after cocaine (123+/-6.6%), phentolamine (415+/-93%) and phenoxybenzamine (578+/-107%). Phentolamine and phenoxybenzamine were much more effective than cocaine in enhancing overflow.3. Before treatment with drugs, flow-stops of 30, 60 and 120 s reduced NA outputs to 70+/-6.6, 27.5+/-2 and 7%, respectively, of the control outputs without flow-stop. None of the drugs significantly influenced the percentage reductions in NA outputs during a 30 s flow-stop. However, the percentage outputs after cocaine or phenoxybenzamine treatment during a 60 s flow-stop significantly increased to 45+/-2.5% and 57+/-6%, respectively, as compared to the percentage output of 27.5+/-2% from untreated spleens during a corresponding flow-stop period. During flow-stop, there was no appreciable metabolism of the released transmitter.4. Diffusion of the released transmitter from the site of liberation plays only a minor role in the removal of the released NA.5. It is suggested that the NA released by nerve stimulation acts on the presynaptic alpha sites to inhibit its own release by a negative feedback mechanism. Adrenoceptor blocking agents enhance the NA overflow from spleen because they remove this autoinhibition by blocking the presynaptic alpha sites.

UI MeSH Term Description Entries
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
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
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D010643 Phenoxybenzamine An alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. Dibenylene,Dibenyline,Dibenziran,Dibenzylin,Dibenzyline,Dibenzyran,Phenoxybenzamine Hydrochloride,Hydrochloride, Phenoxybenzamine
D010646 Phentolamine A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. Fentolamin,Phentolamine Mesilate,Phentolamine Mesylate,Phentolamine Methanesulfonate,Phentolamine Mono-hydrochloride,Regitine,Regityn,Rogitine,Z-Max,Mesilate, Phentolamine,Mesylate, Phentolamine,Methanesulfonate, Phentolamine,Mono-hydrochloride, Phentolamine,Phentolamine Mono hydrochloride
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D003042 Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005246 Feedback A mechanism of communication within a system in that the input signal generates an output response which returns to influence the continued activity or productivity of that system. Feedbacks
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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