Mode of Action of Partial Agonists on the Taenia Caecum of the Guinea Pig and Drug-Receptor Theory

Takagi, Keijiro; Takayanagi, Issei

doi:10.1254/jjp.19.520

Cited by 6 publications

(5 citation statements)

References 10 publications

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“…Furthermore, papaverine and dodecyl trimethylammonium (8), which relaxed the intestinal smooth muscle of the guinea pig, contracted the denervated muscle.…”

Section: Discussionmentioning

confidence: 95%

Effects of Some Divalent Cations on the Denervated Skeletal Muscle of the Rat

1972

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There have been few studies on actions of divalent cations on mammalian skeletal muscles (1) as compared to amphibian muscles, which have been used in the study of the role of calcium in the excitation-contraction coupling process (2, 3). Related studies on mam malian denervated skeletal muscle are also few.
Denervated skeletal muscles were generally reported to be more sensitive to acetyl choline (ACh) (4, 5), but Kiku-iri (6) indicated that twitch and tetanus evoked by direct electrical stimulation were reduced gradually with the lapse of time after denervation in the sartorius muscle of the frog, while the pattern of caffeine-contracture in the denervated muscle was not different from that in the innervated muscle. Gutmann and Sandow (7) reported that a decrease in twitch and tetanus tensions became progressivly greater with increased duration of denervation in the extensor digitorum longus muscle of rats, whereas the denervated muscle became more sensitive to caffeine.
The aim of the present study was to investigate effects of some divalent cations, electri cal stimulation and substituting strontium ions for calcium ions in the bath solution on the rat denervated skeletal muscle. METHODSMale rats of the Wistar strain were denervated, under ether anesthesia, by removing approx. 1.5 cm of obturator nerve in the abdomen supplying the gracilis anticus muscle.These were maintained postoperatively for 15-26 days. The average size of the muscle preparations was 0.5-1.0 mm x 2 mm x 15 mm (thickness x width x length). The isolated muscle was suspended in a 12 ml organ bath filled with Locke-Ringer solution gassed with a mixture of 98 % 0, and 2 % CO, and kept at 32°e. In order to stimulate the muscle electrically, massive electrodes were used and the rectangular current pulses of 1 msec duration and of sufficent strength to produce the supramaximal contraction were applied.In this experiment Locke-Ringer solution containing d-tubocurarine (10_1 mM) was used as bath fluid to eliminate indirect action. The Locke-Ringer solution had the following composition (mM

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“…Furthermore, papaverine and dodecyl trimethylammonium (8), which relaxed the intestinal smooth muscle of the guinea pig, contracted the denervated muscle.…”

Section: Discussionmentioning

confidence: 95%

Effects of Some Divalent Cations on the Denervated Skeletal Muscle of the Rat

1972

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“…In some experiments, a modified locke Ringer solution was used, in which NaCI and Na HCO, were replaced by KC1 and KHCO3 (5). This modified Locke Ringer solution was called "K-Locke Ringer solution" in this paper.…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, some partial agonists in a series of cholinergic drugs contract the isolated taenia caecum (or taenia coli) of the guinea pig and at the same time the contrac tion which they produce is inhibited by their non-secific inhibitory action, so that maximal responses to partial agonists are smaller than that to full agonists (3)(4)(5). Furthermore, ephedrine which was classified as an adrenergic partial agonist relaxes the taenia caecum and at the same time the relaxation which it produces is antagonized by its own excitatory action, so maximal relaxation by it is smaller than that by a full agonist, epinephrine (5).…”

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Beta-Adrenergic Receptors in Various Organs

Takagi

Takayanagi

1970

Japanese Journal of Pharmacology

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The concept of two adrenergic receptor mechanisms or a and (3-adrenergic receptor systems, originally postulated by Ahlguist (1) is presently accepted. Furchgott (2) has presented evidence suggesting that there may be different types of receptors in the (3 class. This conclusion was based on differences in relative potencies of isoprenaline, epinephrine, norepinephrine and phenylephrine in variety of isolated organs.On the other hand, some partial agonists in a series of cholinergic drugs contract the isolated taenia caecum (or taenia coli) of the guinea pig and at the same time the contrac tion which they produce is inhibited by their non-secific inhibitory action, so that maximal responses to partial agonists are smaller than that to full agonists (3-5). Furthermore, ephedrine which was classified as an adrenergic partial agonist relaxes the taenia caecum and at the same time the relaxation which it produces is antagonized by its own excitatory action, so maximal relaxation by it is smaller than that by a full agonist, epinephrine (5). DCI was also reported as an adrenergic partial agonist (6-8). However, mode of action of DCI is not precisely examined. The purpose of this paper is to compare the activities of some i9-adrenergic blockers in various organs and to determine if there are different types of the Q-adrenergic receptors in the organs. Furthermore, mode of action of DCI which is known as a dualist on some organs was precisely tested. METHODSA piece of the taenia caecum (or taenia coli), atrium and tracheal muscle (9) from the male guinea pig (300 to 350 g in body weight) and a piece of the jejunum and the fundus of the stomach from the male rat (150 to 200 g in body weight) prepared by Vane's method (10) were suspended in a 30 ml organ bath. The responses of these preparations to the drugs were recorded through an isotonic lever.The responses of the uterus from the castrated rat (150 to 200 g in body weight) sus pended in the same organ bath was isometrically recorded through a mechano-electrical transducer (RCA-5734). Locke Ringer solution gassed with a mixture of 95% 02 and 5 % CO, and kept at 32°C was used as a bath fluid. Locke Ringer solution used contained 9.0 g of NaCI, 0.4 g of KCI, 0.2 g of CaC12j 0.2 g Of MgC12, 0.2 g of NaHCO, and 0.5 g of glucose in a litre.

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“…Dikstein and Sulman (1) postulated that the inhibitory effect of acetone was due to the extraction of phospholipids from the organ, but Ehrenpreis, Hazra and Bigo-Gullino It has been suggested that the mechanism of action of papaverine is concerned with the inhibition of supply of calcium ions to the contractile element of the smooth muscle (9)(10)(11). Sunano and Miyazaki (12) have presented evidence that acetone may induce the change in permeability of calcium ions through the cell membrane of the guinea pig taenia caecum (or taenia coli).…”

Section: Membrane Activitymentioning

confidence: 99%

Effect of Calciumions and Phospholipids on Antiacetylcholine Action of Acetone and Papaverine

Takagi

Takayanagi

Kubota

et al. 1970

Japanese Journal of Pharmacology

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Dikstein and Sulman (1) reported that the treatment of the rectus abdominis muscle of Bufo viridis toad with 3.4 M (25%) acetone for 2 minutes eliminated the response of the muscle to acetylcholine (ACh), but 5 to 20 ag/ml of phospholipids such as phospha tidylserine could restore the response of the treated muscle to ACh. They also observed similar effects of phospholipids on the rabbit uterus treated with acetone and restoration of the response of the ileum to norepinephrine after the treatment with phospholipids, and postulated that the phospholipids of receptors were extracted by acetone and could be replaced by those from an exogenous source.In a recent report, however, Ehrenpreis, Hazra and Bigo-Gullino (2) presented evi dence that smooth muscles of various organs treated with 3.4 M (25%) acetone were not restored in their responses to agonists by application of phospholipids, and the effect of acetone was concerned with the denaturation of the receptor protein by acetone, but not with lipid extraction from the receptor.We have found in this paper that the mode of action of acetone is very similar to that of papaverine. The aims of this paper are to study the mechanism of antiacetylcholine action of acetone and papaverine, and to test the restoration of the response of the papa verine or acetone-treated ileum to ACh by phospholipids. Also in our experiments, as described by Ehrenpreis, Hazra and Bigo-Gullino (2), 3.4 M (25%) acetone applied for 2 minutes at 32°C abolished the response of ileum to ACh, and even large doses of phospholipids could not restore the responsiveness of the ileum after the acetone treatment. In an ileum maintaining a moderate response to ACh after the acetone treatment under milder conditions, however, various phospholipids could restore distinctly the responsiveness of the ileum. MATERIALS AND METHODSAfter killing an adult male guinea pig by a blow on the head, small intestine was isolated and the ileum approximately 3 cm length was suspended in a 30 ml organ bath

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Mode of Action of Partial Agonists on the Taenia Caecum of the Guinea Pig and Drug-Receptor Theory

Cited by 6 publications

References 10 publications

Effects of Some Divalent Cations on the Denervated Skeletal Muscle of the Rat

Effects of Some Divalent Cations on the Denervated Skeletal Muscle of the Rat

Beta-Adrenergic Receptors in Various Organs

Effect of Calciumions and Phospholipids on Antiacetylcholine Action of Acetone and Papaverine

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