There is no direct relationship between PI response and smooth muscle contraction of rat trachea stimulated by {alpha}-agonists

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There is no direct relationship between PI response and smooth muscle contraction of rat trachea stimulated by ${alpha}$ -agonists

Osamu Shibata, MD, Masataka Saito, MD, Takuji Maekawa, MD, Singo Shibata, MD, Tetsuji Makita, MD and Koji Sumikawa, MD

Nagasaki, Japan

To the Editor:

${alpha}$ -Adrenoceptor agonists are commonly used during anesthesia tocause vascular smooth muscle contraction through the activationof phosphatidylinositol (PI) response. Meurs et al. have demonstratedevidences for a direct relationship between PI response andairway smooth muscle contraction induced by muscarinic agonists.¹Although ₁ ${alpha}$ -adrenoceptors exist in the airway smooth muscle,²the signal transduction of ₁ ${alpha}$ -adrenoceptors in the airway isnot fully understood. The present study was designed to clarifywhether ₁ ${alpha}$ -adrenoceptor agonists could stimulate PI response,resulting in an induction of airway smooth muscle contractionof rat trachea.

Rat tracheal rings were suspended between two stainless hooksin Krebs-Henseleit (K-H) solution. Contraction was induced withcarbachol (a muscarinic agonist), phenylephrine and norepinephrine.The tracheal slices were incubated in K-H solution containingLiCl and ³[H]myo-inositol in the presence of carbachol, phenylephrineor norepinephrine. ³[H]inositol monophosphate (IP₁)³^,⁴ a degradationproduct of PI response, was measured.

Carbachol caused tracheal ring contraction at a dose of 0.1µM or greater, whereas phenylephrine or norepinephrinecould not cause the contraction. Carbachol caused IP₁ accumulationat a dose of 1 µM or greater, and phenylephrine and norepinephrinecaused IP₁ accumulation at doses of 100 µM and 10 µM,respectively. There was a direct relationship between PI responseand airway smooth muscle contraction stimulated by carbachol.However, neither phenylephrine nor norepinephrine could causetracheal ring contraction in spite of increased IP₁ accumulation,suggesting that there is no direct relationship between PI responseand airway smooth muscle contraction stimulated by ₁ ${alpha}$ -adrenoceptoragonists in rat trachea.

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FIGURE The effects of carbachol (CCh), phenylephrine (Phe) and norepinephrine (NE) on resting tension and IP₁ accumulation of rat trachea (mean ± SE; n=8). Bq: becquerel, IP₁: inositol monophosphate, *P <0.05, ***P <0.001 vs 0.

References

1 Meurs H, Roffel AF, Postema JB, et al. Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists. Eur J Pharmacol 1988; 156: 271–4.[Medline]

2 Barnes PJ, Basbaum CB, Nadel JA. Autoradiographic localization of autonomic receptors in airway smooth muscle. Marked differences between large and small airways. Am Rev Respir Dis 1983; 127: 758–62.[Medline]

3 Shibata O, Tsuda A, Makita T, et al. Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs. Can J Anaesth 1998; 45: 1190–5.[Abstract/Free Full Text]

4 Shibata O, Todoroki S, Terao Y, et al. Phosphatidylinositol responses are involved in the vascular effects of thiamylal and fentanyl. Can J Anaesth 1995; 42: 1164–70.[Abstract/Free Full Text]