pituitrin and Epilepsy

This review of the CNS effects of the neurohypophyseal hormones and related neuropeptides discusses recent data illustrating the significance of these principles in brain function, synthesis, distribution, in particular in extrahypothalamic brain structures, binding sites, and signal transduction. Binding sites for vasopressin of the vascular V1a type have been found in the CNS and there is evidence for the existence of a subtype of the antidiuretic V2 receptor in the brain. Also two types of oxytocin binding sites have been detected. One widely distributed throughout the CNS is comparable to the uterine type receptor and a sexually dimorphic slightly different type is found in the ventromedial nucleus. Vasopressin and oxytocin can be converted to highly selective C-terminal fragments as AVP-(4-9) and OXT-(4-9) and shorter fragments. Conversely they can be acetylated. This almost completely blocks intrinsic activity in bioassays for central and peripheral effects. Such modifications are a good example of the plasticity of a neuropeptide system. For a number of CNS effects of the neurohypophyseal hormones, the whole molecule is required, as it is for their endocrine effects. This is the case for the influence of vasopressin on social communication, temperature regulation, epilepsy, and barrel rotation which may be an animal model of febrile convulsions, and some aspects of the central regulation of the cardiovascular system and for oxytocin on sexual behavior, social communication, and grooming. Nonendocrine C-terminal conversion products seem to exert their effects exclusively on the brain. These neuropeptides modulate learning and memory processes, social recognition, and rewarded behavior. The neuroendocrine and neuropeptide effect of vasopressin and oxytocin and related neuropeptides often exert their CNS effects in an opposite way. Neurochemical and electrophysiological studies suggest that norepinephrine, dopamine, serotonin, and glutamate are the neurotransmitters involved in the influence of the neurohypophyseal hormones and related neuropeptides on brain function. It appears that adequate amounts of vasopressin and oxytocin to induce these effects are released at the appropriate sites of action. It is postulated that the mix of neuropeptides released in the brain in response to environmental changes qualifies the behavioral, neuroendocrine, and immune response and the response of the autonomic nervous and vegetative systems of the organism. Althou

Topics: Amino Acid Sequence; Animals; Arginine Vasopressin; Brain; Cardiovascular Physiological Phenomena; Central Nervous System; Epilepsy; Feeding Behavior; Female; Humans; Maternal Behavior; Molecular Sequence Data; Neurons; Neuropeptides; Oxytocin; Pituitary Hormones, Posterior; Receptors, Vasopressin; Social Behavior; Vasopressins

Neuropeptides are sufficiently stable to allow valid radioimmunoassay of peptide concentrations in post-mortem human nervous tissue and in human cerebrospinal fluid. Studies have now documented abnormalities of peptide concentrations in degenerative diseases of the brain. Somatostatin concentration is reduced in the hippocampus and neocortex of patients dying with Alzheimer's type dementia. In Huntington's disease, there are reduced concentrations of substance P, met-enkephalin and cholecystokinin in the basal ganglia; in contrast the concentrations of somatostatin and TRH are increased. Immunocytochemical and experimental lesion studies are underway in an attempt to localize the peptide-containing cells affected by these disorders; and the potential role of alterations in neuropeptide function in the pathogenesis, clinical manifestations and therapy of these illnesses is of great interest. Although alterations of CSF peptide concentrations have been reported in a variety of human diseases, interpretation of these results requires knowledge of the origin and disposition of CSF peptides. Future research into the pathology of peptidergic systems will depend on the development of specific peptide antagonists to probe dynamic aspects of peptide function and on the application of the tools of molecular biology, such as specific mRNA assays, to human material.

Topics: Alzheimer Disease; Animals; Brain; Cholecystokinin; Choline O-Acetyltransferase; Endorphins; Epilepsy; Forecasting; Histocytochemistry; Humans; Huntington Disease; Migraine Disorders; Nerve Tissue Proteins; Nervous System Diseases; Pain; Parkinson Disease; Radioimmunoassay; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Tissue Distribution; Vasopressins

New class of therapies, including bipolar therapies (BPT) and "paradoxical" unipolar therapies (PUT) were firstly proposed in relation to a clinical insight and to some results of biological investigations, then they gave rise to mathematical modeling which brought a justification of these therapies, at least from a theoretical point of view. After recalling the mathematical model for the regulation of agonistic antagonistic couples, and reporting the fundamental types of control simulation by means of it, we point out the validity of therapeutical applications inferred from this model. These therapy modalities, including BPT and PUT, now concern the following diseases: astrocytomas, epilepsia and trials on multiple sclerosis. Even if such attempts are in their early stage, noticeably for the last case where biological changes have mainly been studied, it seems that a large span of treatments is open to BPT and PUT. Improvement of these techniques in the future depends, in our opinion, on a parallel working on the dynamics of the mathematical model and the dynamics, perceived by clinical insight and confirmed by biological investigations, of the body reactions to such strategies. Justification of BPT and PUT was given, by resorting to the notion of "pathological homeostasis" which, too often, intervenes in order to nullify the effects of unilateral (not paradoxical) therapies. This research has elicited some therapies which use two agents with antagonistic effects or only an agent with effects similar to the agent already in excess in the body--in both cases at nearly physiological doses.

Topics: Adaptation, Physiological; Adrenal Cortex Hormones; Animals; Astrocytoma; Brain; Brain Neoplasms; Computer Simulation; Epilepsy; Homeostasis; Humans; Models, Theoretical; Multiple Sclerosis; Vasopressins

A 15-year-old boy with sequelae of perinatal asphyxia experienced intractable startle-induced epileptic seizures, which were transiently suppressed with episodic vomiting. His vomiting was associated with adrenocorticotropin and antidiuretic hormone discharge, and the alteration of urinary catecholamine excretion, which might modulate epileptic seizures. Because startle-induced epileptic seizures are resistant to conventional antiepileptic therapy, this case is informative for the treatment of startle epilepsy.

Topics: Adolescent; Adrenocorticotropic Hormone; Epilepsy; Humans; Male; Reflex, Startle; Secretory Rate; Vasopressins; Vomiting

Serum levels of 7 hormones and neuropeptides were studied in the course of development of a generalized epileptic activity (EA) induced in rats by intraperitoneal administration of corasole (75 mg/kg), i.e. 30 s (latent period), 50-150 s, 5-10 min after epileptogenic administration. A significant increase in the levels of ACTH (5.2-fold), glucagon (1.8.-fold), angiotensin I and renin activity were shown to occur 90-180 s later. Further on in the course of EA the level of ACTH remained enhanced but the level of glucagon and renin-angiotensin activity returned to normal. The levels of cortisol, vasopressin and aldosterone were enhanced 2-3-fold 30 min later. The level of insulin 30 min later remained unchanged. The role of neuropeptides and hormones in the onset and suppression of EA is discussed.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Aldosterone; Angiotensin I; Animals; Epilepsy; Glucagon; Hydrocortisone; Male; Neuropeptides; Rats; Renin; Vasopressins

As more small peptidergic components of the central nervous system are isolated, their role in disease states is being investigated. Several of these neuropeptides, especially the opioidlike peptides, adrenocorticotropic hormone, and some hypothalamic releasing factors, have been found to alter neuronal excitability. This finding has led to the proposal that these peptides may play a role in the pathogenesis of the epilepsies. We tested this hypothesis in a genetic model of epilepsy. At nontoxic doses, several exogenously administered peptides had anticonvulsant properties, while others were proconvulsant. The most potent anticonvulsant was the opioidlike peptide beta-endorphin. Its effect was similar to that of the opioid alkaloids. Using the potent antagonist naloxone hydrochloride to block possible endogenous opioid-like peptides, we found no effects on seizures in naive animals. Naloxone did alter postictal events, however, by partially blocking the postictal refractoriness to further seizures. We speculate that one possible role for the endogenous opioid peptides may be to limit the spread of seizures or to modulate postictal susceptibility to further seizures. Naloxone was effective in this model only after stressful situations occurred that modified the seizures and presumably induced a release of endogenous opioidlike peptides. Support for this hypothesis from other epilepsy models is discussed. Other peptidergic systems may also be active in various epileptic models, and the current understanding of their roles is reviewed.

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Brain; Endorphins; Epilepsy; Gerbillinae; Naloxone; Peptide Fragments; Receptors, Opioid; Synaptic Transmission; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Acute Disease; Adult; Ataxia; Barbiturates; Consciousness Disorders; Craniocerebral Trauma; Electroencephalography; Epilepsy; Female; Humans; Hyponatremia; Nystagmus, Pathologic; Porphobilinogen; Porphyrias; Urinary Incontinence; Vasopressins; Water-Electrolyte Balance

Topics: Animals; Automatism; Brain; Electroencephalography; Epilepsy; Humans; Movement; Pattern Recognition, Automated; Rats; Sleep; Vasopressins; Wakefulness

Topics: Animals; Brain; Diuretics; Electroencephalography; Epilepsy; Erythrocytes; Humans; Rats; Sodium; Vasopressins; Water; Water-Electrolyte Balance

Topics: Agenesis of Corpus Callosum; Cerebral Ventriculography; Child; Child, Preschool; Diabetes Insipidus; Drinking Behavior; Dwarfism, Pituitary; Electroencephalography; Epilepsy; Humans; Hypothermia; Male; Puberty, Precocious; Recurrence; Vasopressins

Topics: Adult; Chlorides; Diagnosis, Differential; Epilepsy; Female; Humans; Hypertension; Hyponatremia; Porphyrias; Porphyrins; Pregnancy; Puerperal Disorders; Vasopressins

Topics: Adolescent; Adult; Diuretics; Electroencephalography; Epilepsy; Female; Humans; Male; Middle Aged; Vasopressins; Water; Water-Electrolyte Balance

Topics: Adult; Anticonvulsants; Calcium; Chlorides; Chronic Disease; Creatinine; Epilepsy; Female; Humans; Intellectual Disability; Male; Mass Screening; Metabolic Clearance Rate; Middle Aged; Osmolar Concentration; Phenobarbital; Phenytoin; Potassium; Sodium; Specific Gravity; Time Factors; Urea; Urine; Vasopressins; Water-Electrolyte Balance

Topics: Adrenocorticotropic Hormone; Androgens; Arginine Vasopressin; Cerebral Cortex; Cortisone; Desoxycorticosterone; Electroencephalography; Epilepsy; Pharmacology; Toxicology; Vasopressins; Water Intoxication; Water-Electrolyte Balance

Topics: Bipolar Disorder; Depression; Epilepsy; Estrogens; Female; Humans; Hydantoins; Intellectual Disability; Mental Disorders; Mentally Ill Persons; Nitrates; Potassium; Premenstrual Syndrome; Progesterone; Schizophrenia; Thyroid Hormones; Tranquilizing Agents; Vasopressins

Topics: Epilepsy; Humans; Vasopressins

Topics: Epilepsy; Humans; Pentylenetetrazole; Pituitary Hormones; Vasopressins

Topics: Epilepsy; Humans; Vasopressins

Topics: Brain; Electroencephalography; Epilepsy; Humans; Vasopressins