L- and DL-carnitine induce tetanic fade in rat neuromuscular preparation.

Carnitine, a structurally choline-like metabolite, has been used to increase athletic performance, although its effects on neuromuscular transmission have not been investigated. It is present in skeletal muscle and its plasma levels are about 30 to 90 micro M. Using rat phrenic nerve diaphragm preparations indirectly and directly stimulated with high rate pulses, D-carnitine (30 and 60 micro M), L-carnitine (60 micro M) and DL-carnitine (60 micro M) were shown to induce tetanic fade (D-carnitine = 19.7 +/- 3.1%, N = 6; L-carnitine = 16.6 +/- 2.4%, N = 6; DL-carnitine = 14.9 +/- 2.1%, N = 6) without any reduction of maximal tetanic tension. D-carnitine induced tetanic fade in neuromuscular preparations previously paralyzed with d-tubocurarine and directly stimulated. The effect was greater than that obtained by indirect muscle stimulation. Furthermore, previous addition of atropine (20 to 80 micro M) to the bath did not reduce carnitine isomer-induced tetanic fade. In contrast to D-carnitine, the tetanic fade induced by L- and DL-carnitine was antagonized by choline (60 micro M). The combined effect of carnitine isomers and hemicholinium-3 (0.01 nM) was similar to the effect of hemicholinium-3 alone. The data suggest that L- and DL-carnitine-induced tetanic fade seems to depend on their transport into the motor nerve terminal.

[1]  K. Broadley,et al.  Muscarinic Receptor Agonists and Antagonists , 2001, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry.

[2]  J. Nezu,et al.  Molecular and Functional Characterization of Organic Cation/Carnitine Transporter Family in Mice* , 2000, The Journal of Biological Chemistry.

[3]  J. Gómez-Reino,et al.  Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy. , 1996, Arthritis and rheumatism.

[4]  R. Bellasio,et al.  Reye syndrome model in rats: protection against liver abnormalities by L-carnitine and acetyl-L-carnitine. , 1995, The Journal of pharmacology and experimental therapeutics.

[5]  J. Arenas,et al.  Muscle carnitine deficiency and lipid storage myopathy in patients with mitochondrial myopathy , 1993, Muscle & nerve.

[6]  J. Arenas,et al.  Plasma carnitine insufficiency and effectiveness of L‐carnitine therapy in patients with mitochondril myopathy , 1993, Muscle & nerve.

[7]  I. Wessler,et al.  Acetylcholine at motor nerves: storage, release, and presynaptic modulation by autoreceptors and adrenoceptors. , 1992, International review of neurobiology.

[8]  T. Saheki,et al.  Animal model of systemic carnitine deficiency: Analysis in C3H-H-2° strain of mouse associated with juvenile visceral steatosis , 1991 .

[9]  N. Vaziri,et al.  Intestinal absorption of carnitine in experimental azotemia. , 1990, Research communications in chemical pathology and pharmacology.

[10]  G. Dunea,et al.  Carnitine: An Overview , 1990, The International journal of artificial organs.

[11]  E. Gorostiaga,et al.  Decrease in respiratory quotient during exercise following L-carnitine supplementation. , 1989, International journal of sports medicine.

[12]  R. Chesney.  Clinical Aspects of Human Carnitine Deficiency , 1987 .

[13]  A. Corrado,et al.  Reversal by Atropine of Tetanic Fade Induced in Cats by Antinicotinic and Anticholinesterase Agents , 1987, Anesthesia and analgesia.

[14]  R. Rylett,et al.  An Evaluation of Irreversible Inhibition of Synaptosomal High‐Affinity Choline Transport by Choline Mustard Aziridinium Ion , 1984, Journal of neurochemistry.

[15]  J. Bremer.  Carnitine--metabolism and functions. , 1983, Physiological reviews.

[16]  F. Nagle,et al.  Effects of acute moderate-intensity exercise on carnitine metabolism in men and women. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[17]  F. Nagle,et al.  THE EFFECTS OF EXERCISE TRAINING ON CARNITINE STATUS AND PHYSICAL WORK CAPACITY IN DIALYSIS PATIENTS , 1982 .

[18]  P. Borum,et al.  Carnitine biosynthesis: nutritional implications. , 1982, Advances in nutritional research.

[19]  W. Bowman.  Prejunctional and Postjunctional Cholinoceptors at the Neuromusclar Junction , 1980, Anesthesia and analgesia.

[20]  C. Rebouche,et al.  Tissue distribution of carnitine biosynthetic enzymes in man. , 1980, Biochimica et biophysica acta.

[21]  C. Rebouche.  COMPARATIVE ASPECTS OF CARNITINE BIOSYNTHESIS IN MICROORGANISMS AND MAMMALS WITH ATTENTION TO CARNITINE BIOSYNTHESIS IN MAN1 , 1980 .

[22]  T. Takahashi,et al.  Effects of carnitine administration, fasting, and exercise on urinary carnitine excretion in man. , 1976, Journal of nutritional science and vitaminology.

[23]  J. Seifter,et al.  The pharmacology of d- and l-carnitine and d- and l-acetylcarnitine. Comparison with choline and acetylcholine. , 1971, The Journal of pharmacology and experimental therapeutics.

[24]  E. Bulbring.  Observations on the isolated phrenic nerve diaphragm preparation of the rat. , 1946, British journal of pharmacology and chemotherapy.

[25]  A. Rosenblueth,et al.  CURARIZATION, FATIGUE AND WEDENSKY INHIBITION , 1937 .