Selective inhibition by dantrolene of caffeine-induced catecholamine release from perfused dog adrenals. 1987

K Sumikawa, and Y Hayashi, and K Fukumitsu, and I Yoshiya
Department of Anesthesiology, Toyonaka Municipal Hospital, Osaka, Japan.

Effects of dantrolene sodium on catecholamine (CA) release from the perfused dog adrenal medulla was investigated in relation to it's therapeutic action on malignant hyperthermia (MH), in which CAs would play a significant pathophysiological role. Acetylcholine (ACh)-induced CA release was not affected, whereas caffeine-induced CA release was inhibited by dantrolene in a dose-dependent manner (84% inhibition at 10 microM). Dantrolene had no effect on the CA release induced by lasalocid or Na+ deprivation. On the other hand halothane inhibited ACh-induced CA release markedly, Na+ deprivation-induced CA release slightly, but not caffeine-induced CA release at all. The results indicate that dantrolene selectively inhibit caffeine-induced CA release, and that the therapeutic action of dantrolene on MH would be, at least in part, due to inhibition of abnormal release of Ca2+ in the adrenal medullary cells.

UI MeSH Term Description Entries
D008297 Male Males
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D002110 Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling. 1,3,7-Trimethylxanthine,Caffedrine,Coffeinum N,Coffeinum Purrum,Dexitac,Durvitan,No Doz,Percoffedrinol N,Percutaféine,Quick-Pep,Vivarin,Quick Pep,QuickPep
D002395 Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from TYROSINE. Catecholamine,Sympathin,Sympathins
D003620 Dantrolene Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. Dantrium,Dantrolene Sodium,Sodium, Dantrolene
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
D006221 Halothane A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178) 1,1,1-Trifluoro-2-Chloro-2-Bromoethane,Fluothane,Ftorotan,Narcotan
D000311 Adrenal Glands A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS. Adrenal Gland,Gland, Adrenal,Glands, Adrenal
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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