Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injection of the neuropeptide, endothelin-1 (ET, range of 3-9 pmol), into a lateral ventricle (ICV) of rats produced barrel rolling and other convulsions including ataxia, forelimb and facial clonus, nystagmus, and tonic extension of the tail and hindlimbs. Using the quantitative autoradiographic [14C]deoxyglucose method, we resolved the focal hypermetabolic correlates of the convulsive activity in numerous brain regions. The present study tested whether the effects of ET were dose dependent by assessing 13 behavioral, 9 physiological, and brain metabolic responses in six individual structures of rats treated separately with ICV ET in doses between 1.5 and 18 pmol. Barrel-rolling convulsions, having a threshold for onset at 3 pmol, displayed increased incidence and severity, and a shorter latency to onset, with the higher ET doses. Within 10-20 min, ET evoked dose-dependent increases in mean arterial pressure and plasma glucose levels, and a significant reduction in arterial PCO2. Among brain structures, the periventricular caudate nucleus near the injection site had an elevated rate of glucose metabolism (+60%) at a 3 pmol threshold. The substantia nigra pars reticulata, medial terminal nucleus of the accessory optic tract, rostral lamella of the inferior olivary nucleus, cerebellar paramedian lobule, and cerebellar copula pyramis, all of which have moderate to dense populations of ET-1 receptors and are related by anatomical connections, displayed significant metabolic stimulation by 9 pmol ET (+47 to +122%). The behavioral, physiological, and focal hypermetabolic effects of the central ET appear to be time coordinated, interrelated, and dose dependent. Identification of the threshold dose for central actions of ET at 3 pmol ICV reveals this peptide as the most potent neuroactive substance yet described in vivo.
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PMID:Dose-related potent brain stimulation by the neuropeptide endothelin-1 after intraventricular administration in conscious rats. 761 31

The neuroactive peptide endothelin-1 has receptors distributed abundantly among subdivisions and nuclei of the visuovestibular and oculomotor systems. In previous work, we and others described the convulsive manifestations resulting from central injection of this neuropeptide, including nystagmus, oculoclonus, exophthalmos, tonic hindlimb extension, and a generalized repetitive motor disturbance called barrel-rolling. We applied the quantitative, autoradiographic [14C]deoxyglucose method to examine the hypothesis that visuovestibular and oculomotor structures would become metabolically stimulated when endothelin was introduced into the brain via the ventricular system in conscious rats. Since previous work had demonstrated that hypermetabolic responses to endothelin in other neural systems were inhibited by an antagonist of neuronal calcium L-type channels, nimodipine, we further tested whether the increased function of vestibulooculomotor nuclei whose metabolic activity was sensitive to endothelin could be altered following nimodipine pretreatment via the ventricle. A single unilateral injection of endothelin (9 pmol in 3 microliters saline) into a lateral ventricle provoked significantly increased rates of glucose metabolism in 22 of 39 individual anatomical structures of the visuovestibular and oculomotor systems. Among those affected were the superficial stratum of the caudal superior colliculus (+25%), the optic tract bilaterally (+35 to 43%), the oculomotor cranial nerve nuclei (III, IV, VI; range of +21 to 47%), and the medial terminal nucleus of the accessory optic tract which harbors dense fields of endothelin binding sites (bilateral increase of +70 to 96%). Several other nuclei involved in the proprioceptive and visuovestibular disturbance caused by endothelin displayed increased metabolic activity, including the cuneate, gracile, sensory trigeminal, and prepositus hypoglossal nuclei, the vestibular subnuclear system, and the cerebellar flocculus. Identification of hypermetabolic responsivity to endothelin in these structures provides further information on the anatomical substrates mediating the behavioral phenomenology of endothelin-induced motor convulsions which involve the paroxysmal participation of the extraocular muscles and motor control systems producing barrel-rolling convulsions. Nimodipine pretreatment inhibited both the convulsive activity and the cerebral hypermetabolic responses to intraventricular endothelin. The results indicate that the neural systems sensitive to intraventricular endothelin become functionally active via a calcium-mediated process that may involve the neuropeptide as an intrinsic signaling molecule.
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PMID:Metabolic and neuroanatomical correlates of barrel-rolling and oculoclonic convulsions induced by intraventricular endothelin-1: a novel peptidergic signaling mechanism in visuovestibular and oculomotor regulation? 822 65

The effects of an endothelin ET(A)-receptor selective antagonist, S-0139, were examined using dogs given endothelin-1 (ET-1) into the subarachnoid space. ET-1 at 40 pmol apparently constricted the basilar artery in anesthetized dogs and caused various grades of ataxia, facial clonus, nystagmus and other features in conscious dogs, partially mimicking those which have been reported for conscious rats. S-0139 could completely inhibit both the vasoconstriction and behavioral changes. It could also alleviate the behavioral changes caused by ET-1 in conscious dogs when given after the severe ataxia. We concluded that ET-1 in the subarachnoid space produces behavioral changes via endothelin ET(A)-receptor mediation similar to its cerebral vasoconstricting action, at least, in dogs.
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PMID:Effects of an endothelin ET(A)-receptor antagonist, S-0139, on cerebral vasospasm and behavioral changes in dogs intracisternally administered endothelin-1. 951 5