The effect of cold storage on the inhibitory action of isoprenaline, phenylephrine and nicotine on the mechanical and membranal activities of guinea-pig taenia caecum.

Abstract

1. The effects of prolonged cold storage on the mechanical and membranal responses to stimulation of alpha- and beta-adrenoceptors by phenylephrine and isoprenaline, respectively, were studied on the guinea-pig taenia caecum.2. Cold storage invariably caused a decrease in the resting membrane potential, and this effect was enhanced as the duration of treatment was prolonged.3. After cold storage (18 days) the tissue potassium ion content (89.7 +/- 1.7 mmol/kg wet wt.) was decreased to 30.5 +/- 1.9 mmol/kg wet wt. whereas that for sodium (69.2 +/- 1.4 mmol/kg wet wt.) increased to 134.0 +/- 2.3 mmol/kg wet wt.4. In the fresh preparations, phenylephrine (1 and 2 muM) caused a cessation of spontaneous action potentials, accompanied by hyperpolarization of the membrane and relaxation of the muscle. These effects were markedly diminished after 18 days of cold storage. Isoprenaline (1 and 2 muM) also blocked the action potentials and caused a concomitant muscle relaxation, but in most cases the hyperpolarization was not observed. After 14 days of cold storage these mechanical and membranal changes associated with isoprenaline treatment were not demonstrable in most preparations.5. Nicotine (5 muM and 50 muM) produced a biphasic effect, cessation of the action potential, hyperpolarization and subsequent relaxation followed by a long lasting depolarization, an accelerated discharge of action potentials and an increase in muscle tension. After a few days of cold storage the hyperpolarization effect disappeared but the intensity of the long-lasting depolarization as well as the contractile effects were increased. After cold storage for more than 7 days, nicotine did not affect mechanical or electrical activity.6. Dibutyryl 3'5' cyclic AMP (1 muM to 500 muM) failed to affect the mechanical and electrical activities of taenia caecum.7. Phenylephrine and isoprenaline had no effect on the high potassiumdepolarized taenia.8. These observations suggest that the electro-mechanical effect of an alpha-adrenoceptor stimulant on the guinea-pig taenia caecum is more resistant to cold treatment than that of a beta-adrenoceptor stimulant. This inhibitory system of stimulation of both a- and 8-receptors of guinea-pig taenia caecum may react by different mechanisms. The results also demonstrate that cold storage itself changes the membrane permeability to ions and the tissue ion content (Na+ and K+) of smooth muscle of guinea-pig taenia caecum.