Pharmacologic Analysis of Nicotine and Dimethylphenylpiperazinium on Pacemaker Activity of the Sa Node in the Dog

Chiba, Shigetoshi; Tamura, Kiyoshi; Kubota, Katsumi; Hashimoto, Koroku

doi:10.1254/jjp.22.645

Cited by 12 publications

(5 citation statements)

References 9 publications

(9 reference statements)

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“…These nicotine actions were inhibited by treatment with tetrodotoxin, which blocks neural excitation on the canine atrium as previously reported (7,8). Histamine-induced positive chronotropic and inotropic effects were not influenced by treatment with tetrodotoxin.…”

Section: Methodssupporting

confidence: 78%

“…In the present study, it was demonstrated that both burimamide and metiamide exert cardiac stimulating proper ties via the tyramine-like action, as burimamide usually caused positive chronotropic and isotropic effects which were completely blocked by alprenolol or desmethylimipramine (7,22). Moreover, although metiamide induced positive chronotropic and inotropic effects less potent than burimamide, these metiamide-induced positive effects were also inhibited by alprenolol or desmethylimipramine, indicating its tyramine-like action.…”

Section: Discussionmentioning

confidence: 51%

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Absence of Blocking Effect of Burimamide and Metiamide on Positive Chronotropic and Inotropic Responses to Histamine in Isolated Dog Atrium

Chiba

1977

Japanese Journal of Pharmacology

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Abstract-Whenhistamine was injected into the sinus node artery of isolated dog atrium perfused with arterial blood led from a carotid artery of the heparinized support dog, positive chronotropic and inotropic effects were dose-relatedly induced at a dose range of 0.1 to 100 Pg. The threshold dose for inducing these positive effects was approximately 0.3 ; eg. These positive responses to histamine were not blocked by tetrodotoxin, desmethylimipramine and alprenolol.These positive effects of histamine were also not significantly influenced by treatment with a histamine H2 receptor an tagonist, burimamide or metiamide.However, these histamine-induced positive chronotropic and inotropic effects were significantly suppressed by an adequate dose of histamine 1-11 receptor antagonist, tripelennamine or diphenhydramine, which enhanced the actions of norepinephrine.From these results, it is suggested that in the dog atrium, histamine causes positive chronotropic and inotropic effects via his tamine H1 receptors. (1-4). However, in isolated dog heart, there is no available report for existence of histamine H2 receptors.Thus, in the present experiments, an attempt was made to investigate the characteristics of cardiac histamine receptors in isolated dog atrium by means of the selective histamine H2 receptor blocking agents, burimamide or metiamide, using the isolated, blood-perfused atrium preparation of the dog (5, 6). Moreover, the action of histamine was analysed by use of pharmacological key drugs, i.e., histamine H1 receptor antagonists (tripelennamine and diphenhydramine), alprenolol which is a potent adrenergic beta-receptor blocking agent, desmethylimipramine which blocks uptake mechanism in the sympathetic nerve terminals, and tetrodotoxin which blocks nerve excitation. MATERIALS AND METHODSTwenty-five mongrel dogs, weighing 11-16 kg, were anesthetized with sodium pen

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Section: Methodssupporting

confidence: 78%

Section: Discussionmentioning

confidence: 51%

Absence of Blocking Effect of Burimamide and Metiamide on Positive Chronotropic and Inotropic Responses to Histamine in Isolated Dog Atrium

Chiba

1977

Japanese Journal of Pharmacology

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“…and inotropic effects were produced. These nicotine-induced effects were significantly suppressed by pretreatment with tetrodotoxin, but tyrarnine-induced effects were not so influenced as reported previously (11,12). Effects of 30-100 pg of 5-HT were not affected by 3-10 pg of tetrodotoxin in 2 preparations, although effects of 1-10 ,ug of nicotine were clearly suppressed.…”

Section: Absence Of Blocking Effect Of Tetrodotoxin On the 5-ht-inducsupporting

confidence: 83%

Pharmacologic Analysis of Chronotropic and Inotropic Responses to 5-Hydroxytryptamine in the Dog Heart

Chiba

1977

Japanese Journal of Pharmacology

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Abstract-Inotropic and chronotropic effects of 5-hydroxytryptamine (5-HT) were investigated in twenty-five isolated canine atrial preparations and three isolated paced ventricular preparations which were suspended in the bath and perfused with arterial blood from the carotid artery of the heparinized support dog. 5-HT was administered into the cannulated sinus node artery in a dose range of I to 300 pig. In small doses of I to 3 pig, 5-HT induced a negative chronotropic and inotropic response.At relatively higher doses over 10 ptg, 5-HT induced a biphasic response: a slight negative chrono tropic and inotropic response, followed by a long-lasting positive response. With large doses, only a positive chronotropic and inotropic response was induced in the majority of cases. Even in the ventricular preparations, 5-HT produced a similar response pattern in inotropism.5-HT-induced positive chronotropic and inotropic responses were completely inhibited by pretreatment with an adrenergic beta-blocking agent, propranolol, or a non-depressant beta-blocking agent, carteolol, and desipra mine, but were not influenced by tetrodotoxin treatment. After the treatment with carteolol or despramine, 5-HT-induced negative responses were potentiated.5-HT induced negative chronotropic and inotropic responses were not inhibited by methy sergide and atropine.From these results, it is suggested that 5-HT induces a direct negative chronotropic and inotropic response and an indirect positive response via its tyramine-like action.5-Hydroxytryptamine (5-HT, serotonin) has positive inotropic and chronotropic effects of varying degrees on isolated hearts, atria and isolated papillary muscles of various species (1, 2). In 1964, James (3) reported that 5-HT had only a negative chronotropic effect on the canine sino-atrial (SA) node in vivo, in contrast to its reported acceleratory action in isolated heart preparations. In 1967, Buccino et al. (4) studied effects of 5-HT in cut pa pillary muscles and canine right-heart-bypass preparations with bilateral carotid sinus and vagal nerve resection. They reported that 5-HT increased the average peak tension of cat papillary muscles or dog left ventricles and concluded that 5-HT has a direct positive inotropic effect on mammalian myocardium. Such a postulation was based on the findings that the augmentation in either rate of tension developed or peak isometric tension produced by 5-HT was not accompanied by changes in time to peak tension, differing from actions of norepinephrine (5, 6). However, they did not use pharmacological drugs for the analysis of effects of 5-HT. In 1971, Fillion et al. (7) reported that when using biochemical assay techniques, release of norepinephrine from the dog heart in situ occurred after intravenous and intracoronary administration of 5-HT.In the present study, effects of 5-HT on pacemaker activity and contractility were in

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“…Nicotine causes a release of norepinephrine from postganglionic sympathetic nerve terminals by activating prejunctional nicotinic receptors (Richardson and Woods 1959;Bhagat et al 1968;Lindmar et al 1968). In the heart, either a bolus injection of tyramine or nicotine readily caused a release of norepinephrine, which in turn produced positive chrono-and isotropic effects (Chiba et al 1972;Ren et al 1991). Thus, in the present study, we made an attempt to evaluate vascular responses to nicotine comparing with those to tyramine and norepinephrine.…”

Section: K Kak Izaki and H Yamauchmentioning

confidence: 99%

Nuclear DNA Analysis of the Periampullary Carcinoma Using Cytologic Bile Specimens

Kakizaki

Yamauchi

1991

Tohoku J. Exp. Med.

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Sendai 983KAKIZAKI, K. and YAMAUCHI, H. Nuclear DNA Analysis of the Periampullary Carcinoma Using Cytologic Bile Specimens. Tohoku J. Exp. Med., 1991, 165 (3), [237][238] DNA cytofluorometric analysis of carcinoma cells of the periampullary region was performed using cytologic bile specimens. The materials were obtained from three cases of obstructive jaundice through percutaneous transhepatic biliary drainage tubes. The DNA ploidy histograms of bile samples could be evaluated as well as those of paraffin-embedded tissue samples. DNA analysis using cytologic bile specimens may reveal biological behavior of carcinoma cells and provide useful information for the choice of therapeutic interventions. periampullary carcinoma ; DNA ploidy pattern ; cytologic bile specimen Analysis of nuclear DNA seemed to be a reliable tool to evaluate the biological aggressiveness of pancreatic and periampullary carcinomas (Yamauchi et al. 1989) using tissue samples obtained operatively. However, no studies of DNA analysis of periampullary carcinoma have been performed preoperatively, because it is hard to obtain sufficient specimens for DNA analysis. We tried the DNA analysis of the carcinoma cells collected from the bile specimen by using a cytofluorometric method (Takahama and Kagaya 1988). Briefly, the cell suspension obtained from a bile sample through the percutaneous biliary drainage tube was smeared after staining with diamidino-phenylindole and fluorescence intensity of 100 carcinoma cells for each case was measured with a spectrophotometric microscope. The DNA content of 20 lymphocytes per case served as a reference to establish the 2c level.The DNA histograms and cytologic findings are shown in Fig. 1. Clinical data of the patients were as follows. Patient 1 was a 39-year old male with adenosquamous carcinoma of the pancreas with multiple liver metastases. A bypass operation was carried out on the patient but he died of the primary disease three months after the operation. The DNA ploidy pattern was aneuploid and polyploid. The DNA content was 4.8+ 1.8 c (mean± s.D. ), which was higher than those of the other two cases. Patient 2 was a 62-year old female with well differentiated adenocarcinoma of the common bile duct. Curative resection was performed. DNA histograms of this case showed a near diploid pattern with a peak in the 2c range. The DNA content was 2.8± 1.0 c, which was the lowest in the three cases. Patint 3 was a 76 year-old female who presented obstructive jaundice and died in three months after onset of jaundice. The cytologic examination of bile showed adenocarcinoma, which was aneuploid and had the DNA value of 3.8+ 1.3 c.

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Pharmacologic Analysis of Nicotine and Dimethylphenylpiperazinium on Pacemaker Activity of the Sa Node in the Dog

Cited by 12 publications

References 9 publications

Absence of Blocking Effect of Burimamide and Metiamide on Positive Chronotropic and Inotropic Responses to Histamine in Isolated Dog Atrium

Absence of Blocking Effect of Burimamide and Metiamide on Positive Chronotropic and Inotropic Responses to Histamine in Isolated Dog Atrium

Pharmacologic Analysis of Chronotropic and Inotropic Responses to 5-Hydroxytryptamine in the Dog Heart

Nuclear DNA Analysis of the Periampullary Carcinoma Using Cytologic Bile Specimens

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