The supersensitivity of isolated rabbit atria and aortic strips produced by 6-hydroxydopamine.
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Biomedical subjects
Publications and source records attributed to S Shibata.
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In vitro treatment with 6-hydroxydopamine (6-OHDA), but not with oxidized 6-hydroxydopamine, caused transient, positive inotropic and chronotropic responses in the isolated rat atria. In the presence of rat blood plasma, the excitatory effect of 6-hydroxydopamine persisted unless the drug was washed out by fresh medium. 6-Hydroxydopamine failed to elicit the excitative response in the atria obtained from reserpinized rats or rats treated with 6-hydroxydopamine in vivo. In vitro treatment with 6-hydroxydopamine did not cause the development of supersensitivity to noradrenaline. Cocaine and desipramine, but not bretylium, inhibited the excitative action of 6-hydroxydopamine. No tachyphylaxis developed after repeated exposure to 6-hydroxydopamine in vitro. Propranolol, but not phentolamine, blocked the excitatory effect of 6-hydroxydopamine. It is thus concluded that in vitro treatment with 6-hydroxydopamine may cause atrial stimulation by an indirect action involving the release of catecholamines as a result of its displacement at the nerve ending.
1. In the guinea-pig taenia caecum, fluorescent adrenergic fibres terminate in both muscle layers. The density of these fibres is greater in the taenia than in the underlying circular muscle layer. The myenteric plexus and individual ganglion cells are also densely innervated by intensely fluorescent adrenergic nerve fibres.2. After three days of cold storage, the specific fluorescence disappeared from all tissue layers of the taenia caecum and smooth muscle fibres. In contrast, cholinesterase active substances were still demonstrable in all tissue layers even after seven days of cold storage but the density of these substances was decreased.3. Cold storage (3-7 days) decreased the tissue noradrenaline content and did not modify the cholinesterase enzyme activity (4 days).4. In cold stored strips, the inhibitory response to nicotine, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) or electrical transmural stimulation was abolished and enhancement of the contractile response occurred. Cold storage also inhibited the inhibitory action of tyramine. Similar results were observed after reserpine treatment.5. In fresh taenia, the relaxation produced by nicotine, DMPP and electrical transmural stimulation was inhibited by adrenoceptor blocking agents and bretylium. In cold storage preparations, contraction produced by these stimuli was blocked by parasympathetic blocking agents and potentiated by anti-cholinesterase. These results indicate that the inhibitory response to these stimulants is mediated by stimulation of the adrenergic nerve system more than by non-adrenergic nerves; the excitatory effect is probably due to stimulation of cholinergic nerves.6. These results suggest that the adrenergic mechanisms of the taenia caecum are more labile in cold storage than the cholinergic mechanisms. Thus, the inhibitory action of cold storage on the relaxation produced by nicotine, DMPP, and transmural stimulation is probably explained by selective physical degeneration of the adrenergic nerve terminal. Also, enhancement of the contractile response to these stimulants in cold stored preparations is explained by the lack of adrenergic inhibitory mechanisms.
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.
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1. Pretreatment of rabbit aortic strips with bretylium potentiated the contractor response to potassium and tyramine but not to noradrenaline. On the other hand, such pretreatment inhibited the response to nicotine.2. Even in reserpinized or cold stored aortic strips, pretreatment with bretylium enhanced the contractor response to potassium and tyramine.3. Pretreatment of fresh, reserpinized, or cold stored aortic strips with pheniprazine potentiated the contractor response to potassium and tyramine.4. Pretreatment of aortic strips with bretylium or pheniprazine did not potentiate the response to 5-hydroxytryptamine (5-HT).5. The results indicate that both bretylium and pheniprazine potentiate the action of tyramine and potassium, not by presynaptic mechanisms, but by postsynaptic action, causing an increase in the sensitivity of the effector cells to the stimulants.
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