Can we "switch" the emphasis please?

The following is the abstract of the article discussed in the subsequent letter:

	ABSTRACT

Kitaura, Takashi, Naoko Tsunekawa, and Hideo Hatta. Decreased monocarboxylate transporter 1 in rat soleus and EDL muscles exposed to clenbuterol. J Appl Physiol 91: 85-90, 2001.We hypothesized that a shift in muscle fiber type induced by clenbuterol would change monocarboxylate transporter 1 (MCT1) content and activity of lactate dehydrogenase (LDH) and isoform pattern and shift myosin heavy chain (MHC) pattern in soleus (Sol) and extensor digitorum longus (EDL) of male rats. In the clenbuterol-administered rats (2.0 mg · kg¹ · day¹ subcutaneously for 4 wk), the ratio of muscle weight to body weight increased in the Sol (P < 0.05) and the EDL (P < 0.01). Clenbuterol induced the appearance of fast MHC_2D and decreased slow MHC₁ in Sol (13%) but had no effect on EDL. The MHC pattern of Sol changed from slow to fast type. Clenbuterol increased LDH-specific activity (P < 0.01) and the ratio of the muscle-type isozyme of LDH to the heart type (P < 0.05) in Sol. The LDH total activity of the EDL muscle was also increased (P < 0.05). Furthermore, MCT1 content significantly (P < 0.05) decreased in both Sol and EDL (27 and 52%, respectively). This study suggests that clenbuterol might mediate the shift of MHC from slow to fast type and the changes in the regulation of lactate metabolism. Novel to this study is the observation that clenbuterol decreases MCT1 content in the hindlimb muscles and that the decrease in MCT1 is not muscle-type specific. It may suggest that the genetic expressions of individual factors involving slow-type MHC, heart-type isozyme of LDH, and MCT1 are associated with one another but are regulated independently.

	LETTER

To the Editor: Clenbuterol, a ₂-adrenoceptor partial agonist, has been subject to investigation by many research laboratories (1, 3-7). Kitaura et al. (2) report that 4 wk of clenbuterol administration to 8-wk-old Sprague-Dawley rats caused a "slow to fast shift in myosin heavy chain (MHC) expression pattern in soleus muscle." However, if one appropriately examines the literature, then it is apparent that, during maturation, rodent soleus muscle tissue changes from ~40% fast MHC profile to a >90% slow MHC profile during the first 10 mo of life (1, 3-7). It is also apparent that no study to date has examined the impact of clenbuterol on soleus MHC phenotype in mature "adult" soleus. Soleus MHC phenotype is ~30% type IIa at 8 wk of age (3, 4, 7), such that the authors reference to higher ₂-receptor density on slow-type muscle cannot explain the effects of clenbuterol. Kitaura et al. state incorrectly that clenbuterol stimulates a shift from "oxidative to anaerobic glycolysis" when an increase in citrate synthase has been reported (6) and overall the impact of clenbuterol on soleus metabolism is ambiguous.

It is the opinion of this author that the article by Kitaura et al. (2), like all that have come before it (1, 3-7), have incorrectly defined the predominant effect of clenbuterol on MHC expression in soleus because clenbuterol has been administered during a time of phenotype maturation. In fact, clenbuterol would appear to prevent the expression of slow MHC and not, on the whole, stimulate the expression of fast MHC (clenbuterol has a minor and inconsistent impact on type II x/d expression). The relevance of such data to adult skeletal muscle must also be questioned. In conclusion, the manuscript by Kitaura et al. does not accurately refer to the reported effects of clenbuterol on skeletal muscle phenotype nor does it accurately refer to the muscle "genomic" literature. It is the belief of this author that clenbuterol does not cause a simple switching of "slow-type MHC" to "fast-type MHC" but rather influences muscle gene expression in a complex manner that potentially involves the negative regulation of the promoters of type I MHC gene expression.

	FOOTNOTES

10.1152/japplphysiol.01204.2001

	REFERENCES

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2.   Kitaura, T, Tsunekawa N, and Hideo H. Decreased monocarboxylate transporter 1 in rat soleus and EDL muscles exposed to clenbuterol. J Appl Physiol 91: 85-90, 2001[Abstract/Free Full Text].

3.   Kovanen, V, and Suominen H. Effects of age and life-time physical training on fibre composition of slow and fast skeletal muscle in rats. Pflügers Arch 408: 543-551, 1987[ISI][Medline].

4.   Lynch, GS, Hayes A, Campbell SP, and Williams DA. Effects of ₂-agonist administration and exercise on contractile activation of skeletal muscle fibers. J Appl Physiol 81: 1610-1618, 1996[Abstract/Free Full Text].

5.   Stevens, L, Firinga C, Gohlsch B, Bastide B, Mounier Y, and Pette D. Effects of unweighting and clenbuterol on myosin light and heavy chain in fast and slow muscles of rat. Am J Physiol Cell Physiol 279: C1558-C1563, 2000[Abstract/Free Full Text].

6.   Torgan, CE, Etgen GJ, Jr, Kang HY, and Ivy JL. Fiber type-specific effects of clenbuterol and exercise training on insulin-resistant muscle. J Appl Physiol 79: 163-167, 1995[Abstract/Free Full Text].

7.   Zeman, RJ, Ludemann R, Easton TG, and Etlinger JD. Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a ₂-receptor agonist. Am J Physiol Endocrinol Metab 254: E726-E732, 1998.

James A. Timmons, Cardiovascular Department Organon Laboratories Ltd. Newhouse, Glasgow ML1 5SH, Scotland E-mail: j.timmons{at}Organon.nhe.akzonobel.nl