摘要:

This review analyzes the results of recent studies of the actions of cholinomimetic drugs on adrenergic nerve terminals and their implications for the cholinergic link hypothesis. Thus far, evidence suggests that the only possible action of endogenous acetylcholine (ACh) present near noradrenaline (NA) stores is an inhibition of the release of NA from the adrenergic nerve terminals and that NA is released only when the action of acetylcholinesterase in inhibited. Nicotinic agents have been shown to act on adrenergic nerve terminal membranes, a finding that casts doubt on the proposed intraneuronal cholinergic sites for the action of endogenous ACh. Evidence also indicates that the mode of adrenergic neurone blocking action of bretylium and guanethidine is independent of the proposed cholinergic process in NA release. Current findings do not support the proposal that nicotinic agents in higher concentrations interfere with adrenergic neurotransmission. It is therefore concluded that nicotinic agents, in causing the release of NA from adrenergic nerve terminals, are merely exhibiting a pharmacological action and not mimicking the physiological function of ACh, as proposed by the cholinergic link hypothesis.

ISSN:0008-4212    

DOI:10.1139/y80-001

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

The anticonvulsant effect of aminooxyacetic acid (AOAA) was examined on a model of experimental epilepsy (kindling) induced by daily appropriate amygdaloid stimulation in the rat. Doses from 5 to 30 mg/kg were intraperitoneally administered in fully kindled animals 3–4 h before triggering a seizure. At low doses (< 15 mg/kg) AOAA had no effect whereas at higher doses (> 15 mg/kg) it reduced the severity of the generalized kindled seizures in over half the cases, and even sometimes completely blocked them. The inhibition of epileptic activity by AOAA is in accordance with the hypothesis that an increase in GABA level is associated with a reduction of epileptic sensitivity. An unexpected lengthening of the afterdischarge duration was also observed in about 20% of the cases, independently of the amount administered. This fact is discussed in regard to the complex action of AOAA on -γ-aminobutyric acid related enzymes.Finally, since the afterdischarge threshold was shown to be unaffected by the drug, it is suggested that it may act on the afterdischarge propagation rather than at the focal amygdaloid level.

ISSN:0008-4212    

DOI:10.1139/y80-002

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

The effect ofp-chlorophenylalanine (p-CPA) pretreatment on barbital tolerance in the rat as measured by motor impairment on the moving belt test was examined in two separate studies. The first used a 2 × 2 design with doses ofp-CPA (125 mg/kg) or water, and sodium barbital (300 mg/kg) or water. The treatments continued for 28 days with tests every 7 days. Thep-CPA dose used was previously shown to produce and maintain > 95% depletion of brain serotonin (5-HT). Tolerance developed to the test doses, and even greater tolerance to the chronic treatment doses. In both cases thep-CPA slowed the development of tolerance without altering the acute response to the challenge dose of barbital. The second study involved only ap-CPA-barbital group and a water-barbital group. In this case treatment lasted for up to 8 days, with separate subgroups being tested only once each at 2-day intervals, in order to prevent the tests from affecting the rate of tolerance development. This experiment confirmed thatp-CPA slowed the development of barbital tolerance. The present findings provide additional support for the possibility that 5-HT may be involved in the development of tolerance to sedatives (e.g., alcohol, pentobarbital).

ISSN:0008-4212    

DOI:10.1139/y80-003

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

A gas chromatographic method was developed to determine metabolites of antipyrine, norantipyrine (NORA), and 4-hydroxyantipyrine in urine usingp-methylated NORA as internal standard. This method requires no derivatization and has ample sensitivity to determine these metabolites in urine after ingestion of antipyrine, a compound widely used as a hepatic probe of drug oxidation.

ISSN:0008-4212    

DOI:10.1139/y80-004

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

Conjugated catecholamines in the circulation and in peripheral tissues were measured together with free catecholamines in an attempt to investigate whether there arein vivocorrelates to a possible biological role of dopamine sulfate suggested by anin vitrofinding of direct conversion of dopamine sulfate to free norepinephrine by dopamine β-hydroxylase.Following the strong sympathoadrenergic stimulus of surgical stress accompanied by an increase in blood pressure and heart rate, conjugated dopamine showed a twofold rise in arterial plasma (p < 0.005) together with increases of all free catecholamines (0.005 < p < 0.02), while conjugates of noreprinephrine and epinephrine decreased in the circulation (0.01 < p < 0.05). Measurements of arteriovenous differences have shown that release of conjugated dopamine occurred from the adrenal gland during operation along with free catecholamines. However, the venous outflow of conjugated dopamine from liver and kidney did not exceed its arterial influx. Conjugated dopamine, in contrast with other conjugates, is present in adrenals, liver, small intestine, and kidney with higher concentrations than free dopamine in the adrenals (p < 0.01). After ultracentrifugation, the chromaffin granule fraction of the adrenal medulla (site of dopamine β-hydroxylase) contains large amounts of conjugated dopamine (apparently sulfate) suggesting a selective accumulation of dopamine sulfate as a readily available free norepinephrine precursor during stress.These findings establish majorin vivodifferences between peripheral conjugated dopamine and conjugates of norepinephrine and epinephrine. They suggest that there may be biological roles for conjugated dopamine beyond that of a dopamine metabolite.

ISSN:0008-4212    

DOI:10.1139/y80-005

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

Clonidine was administered to isolated guinea pig right atria in order to characterize its chronotropic activity and its interaction with other chronotropic agents at the postjunctional level. Clonidine either had no significant effect (10−7–10−4 M) or decreased (10−3 M) atrial rate. Pretreatment of the atria with clonidine noncompetitively antagonized (10−6–10−4 M) the positive chronotropic actions of isoproterenol, and competitively antagonized (10−4 M) the negative chronotropic actions of pilocarpine. At doses of 10−6or 3 × 10−6 M, clonidine also noncompetitively antagonized the positive chronotropic effects of 4-methylhistamine and glucagon. The results show that clonidine antagonizes both adrenergic and cholinergic influences on atrial rate at the postjunctional level and suggest that the antagonism of adrenergic influences does not involve a direct interaction with β-adrenergic receptors.

ISSN:0008-4212    

DOI:10.1139/y80-006

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

The purpose of this study was to examine the effects of cold acclimation on the dynamics of body water in primates. Six male rhesus monkeys were acclimated for 35 days at 6 °C. Water turnover rate (WTR), biological half-life (t1/23H2O), and total body water (TBW) were estimated by the tritium dilution method. A reduced water intake during the 1st week of cold acclimation was associated with a decrease in water balance (total water input minusWTR). Both drinking and total water input were decreased throughout the cold exposure.WTRwas significantly decreased during the last 3 weeks of cold exposure in spite of an increased caloric consumption, which, in a thermoneutral environment, generally is associated with an increasedWTR. Biological half-life for tritium showed a significant average increase during the cold stress.TBWin relation to body weight was increased during the first 2 weeks of cold exposure and had decreased to its lowest level by day 22. Calculations ofTBWwere independent of whether the radioactive decay curve was obtained over short (minutes) or long (days) time intervals and independent of the degree of acclimation. The major adjustments in water content and water metabolism occurred within 2 weeks of continuous cold exposure at 6 °C. The data suggest that the rhesus monkey may be an adequate primate model for studies of body fluid adjustments induced by chronic cold exposure in primates in general, including man.

ISSN:0008-4212    

DOI:10.1139/y80-007

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

The effect of various α-receptor antagonists on the histamine-induced response of guinea pig ileum, guinea pig heart, and rabbit portal vein have been studied. In guinea pig ileum, an H1receptor system, phenoxybenzamine and dibozane are effective antagonists, phentolamine is a weak antagonist, azapetine is without antagonist effect, and tolazoline is a weak agonist. In the H2system of guinea pig right ventricle, phentolamine and azapetine are antagonists, phenoxybenzamine and dibozane are inactive, and tolazoline is an agonist. All antagonists except tolazoline block the histamine response in portal vein which is believed to be mediated by a receptor of low selectivity. Tolazoline is an agonist in portal vein.

ISSN:0008-4212    

DOI:10.1139/y80-008

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

The kinetics of ADP-induced human platelet shape change have been examined. Initial velocities of platelet shape change were estimated by two methods: (1) the slope of the initial decrease in light transmission through stirred, citrated platelet-rich plasma, and (2) direct examination of platelet morphologies by phase-contrast microscopy. In both cases, a value of the Hill coefficient,NH, significantly greater than 1 is obtained (2.0 ± 0.2 and 1.8 ± 0.2, respectively). The observed elevated value ofNHis not due to a substantial fraction of the ADP being platelet bound, the presence of factors in the plasma, platelet heterogeneity, or the influence of the rate of platelet shape change reversion. Our observations suggest that ADP-induced platelet shape change may be a positively cooperative or "threshold" type response.

ISSN:0008-4212    

DOI:10.1139/y80-009

出版商:NRC Research Press    

年代:1980

数据来源: NRC

摘要:

The responses to noradrenaline (NA) and KCl of carotid arterial strips from spontaneously hypertensive rats (SHR) and three strains of normotensive rats (NR) were compared using tissues obtained from young (5–7 weeks) or older (15–17 weeks) rats. The maximum responses and sensitivity of strips from SHR were less than those of NR in both age groups. Relaxation of maximum NA-induced responses was consistently faster, and relaxation of KCl-induced responses generally slower with strips from SHR. Carotid strips from young SHR showed a greater dependence on extracellular calcium in their responses to NA and a lesser dependence in their KCl-induced responses than tissues from NR. We conclude that the smooth muscle of carotid arteries from SHR differs intrinsically from that of NR and that the differences in vascular responses may be related to altered excitation-contraction processes in the SHR.

ISSN:0008-4212    

DOI:10.1139/y80-010

出版商:NRC Research Press    

年代:1980

数据来源: NRC