摘要:

Hormonally stimulated secretion of ACTH from AtT-20 mouse pituitary tumor cells is a cyclic AMP-mediated process. The presence of inhibitory cholinergic muscarinic receptors on these cells was recently reported, and in this study, the relationship between the activation of these receptors and the consequent inhibition of cyclic AMP formation and ACTH secretion was investigated. The muscarinic agent, oxotremorine, antagonized both cyclic AMP synthesis and ACTH secretion in response to corticotropin-releasing factor (CRF), vasoactive intestinal peptide, a 27-amino acid peptide with an N-terminal histidine and a C-terminal isoleucine amide, and forskolin. Other muscarinic agents, carbachol and bethanechol, had similar inhibitory effects. The cholinomimetics reduced basal (unstimulated) ACTH secretion without decreasing basal cyclic AMP levels, and also antagonized hormone release in response to cyclic AMP-independent agonists such as K+, A-23187, and phorbol ester. Scopolamine reversed the inhibitory effects of the muscarinic agents on basal and stimulated ACTH secretion and cyclic AMP formation. Increasing the extracellular calcium concentration reversed the muscarinic antagonism of basal and CRF-stimulated hormone release without affecting the cyclic AMP response. Pertussis toxin pretreatment attenuated the inhibitory effects of the muscarinic agents on forskolin-stimulated cyclic AMP synthesis and ACTH secretion as well as the inhibitory effect of carbachol on basal ACTH release. The data suggest that cyclic AMP is an essential mediator in the ACTH secretory pathway, but that an alternate cyclic AMP-independent ACTH pathway also exists in the clonal cells, and that both pathways may be modulated by a common postcholinergic receptor mechanism.

ISSN:0008-4212    

DOI:10.1139/y85-118

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The fetal and postnatal activity patterns of different hydrolytic enzymes (alkaline phosphatase, gamma-glutamyltransferase, trehalase, maltase, glucoamylase, lactase, and sucrase) have been examined in mouse renal homogenates. Alkaline phosphatase and gamma-glutamyltransferase activities presented approximately similar changes. They increased from 18 days of gestation up to 30 days after birth. These activities showed marked increases during the 3rd and 4th postnatal weeks. A similar important rise was observed for trehalase activity at the end of the suckling period. Maltase activity increased gradually after birth. Traces of lactase, sucrase, and glucoamylase activities were detected at each developmental stage.

ISSN:0008-4212    

DOI:10.1139/y85-119

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The actions of serotonin and norepinephrine were investigated on spinal motoneurones in isolated, hemisected rat and frog spinal cords. Serotonin and norepinephrine induced slowly developing depolarizations of spinal motoneurones which were frequently preceded by brief, low amplitude hyperpolarizations. Neither the depolarizations nor the hyperpolarizations were attenuated by 20 mMMg2+or tetrodotoxin, although synaptic transmission was blocked in both cases. It thus appears unlikely that the action of serotonin and norepinephrine on spinal motoneurone polarization and results from an indirect action via interneurones.

ISSN:0008-4212    

DOI:10.1139/y85-120

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

A heterologous radioimmunoassay was used to measure the concentration of immunoreactive atrial natriuretic peptide (iANP) in plasma from the femoral artery of eight chloralose anaesthetized dogs. Mitral obstruction which increased left atrial pressure by 11 cmH2O increased plasma iANP from 97 ± 10.3 (mean ± SE) to 135 ± 14.3 pg/mL. Pulmonary vein distension increased heart rate but did not increase plasma iANP. Bilateral cervical vagotomy and administration of atenolol (2 mg/kg) did not prevent the increase in iANP with mitral obstruction. Samples of blood from the coronary sinus had plasma iANP significantly higher than simultaneous samples from the femoral artery confirming the cardiac origin of the iANP. Release of iANP depends on direct stretch of the atrium rather than on a reflex involving left atrial receptors.

ISSN:0008-4212    

DOI:10.1139/y85-121

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The function of histamine in living organisms has interested investigators since its discovery shortly after the turn of the century and consequently has lead to the documentation of volumes of published data. It is rather surprising that the overall understanding of the function of histamine is still scant compared with other mediator substances discovered approximately during the same period of time. Perhaps the ubiquitous presence and the many effects of histamine in the body have diluted the efforts of investigators and have prevented a clear definition of all of its function. Both the local actions of histamine as a paracrine transmitter causing indirect responses as well as the multireceptor actions have no doubt also hampered the progress. It has been repeatedly stated that the development of the H2-receptor antagonists was one of the major accomplishments in the histamine field, which has lead to a new wave of increased histamine research activity and provided new meaning to earlier, unexplained data.In a series of symposia initiated by the Canadian Histamine Research Association, an attempt is being made to integrate previous findings with recent advances, and to familiarize those who are interested in histamine with the Canadian investigators and their research areas. The first symposium was held June 14, 1983, in conjunction with the Canadian Federation of Biological Societies and was published in this journal, June, 1984. The present symposium, the second in the series, deals with some aspects of earlier data in light of present knowledge and future prospects, as well as recent observations on receptor action and localization, and the mechanisms of action of drugs involved in the inhibition of histamine release. Because the local action of histamine has posed particular problems for the assessment of histamine concentration in relation to its action, it has become evident that not only histamine concentrations alone but also its metabolites would be of importance to demonstrate a correlation between endogenous histamine and its function. Thus, various assay procedures and methods are reviewed for the measurement of histamine metabolites to illustrate present capabilities in this field.The support for the symposium came from the Canadian Physiological Society, Smith Kline and French Canada Ltd., and Beckman Instruments Inc.

ISSN:0008-4212    

DOI:10.1139/y85-122

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

This review presents, from the author's viewpoint, avenues of histamine research likely to produce new information. One potentially useful approach may be to attempt to relate histamine's function to its occurrence in different body tissues such as the pituitary and hypothalamus, the gastrointestinal mucosa, and the bone marrow and white blood cells. Prospects also seem bright for quantitative studies of histamine metabolites in blood and urine and possible changes in the relative amounts of these metabolites in a variety of diseases.

ISSN:0008-4212    

DOI:10.1139/y85-123

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Early studies suggested that at low temperatures there was a transition of receptor type from an H1to an H2receptor when the temperature was reduced from 37 °C to temperatures below 20 °C. These original observations were based on the development of sensitivity of guinea-pig ileum to the H2antagonist metiamide as the temperature was reduced. More recently, evidence from a number of laboratories has cast doubt on the existence of a simple H1–H2receptor transition, but there is abundant evidence that there are major changes in the response of a variety of smooth muscle preparations to histamine at reduced temperatures. The evidence in regard to alterations in histamine response at low temperatures is reviewed, some new evidence presented, and a model which is consistent with most of the observations is suggested.

ISSN:0008-4212    

DOI:10.1139/y85-124

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Several laboratories have reported ligand binding studies using radioactive histamine H1antagonists to label the H1receptors in mammalian brain. We have extended these studies to a detailed examination of the binding of [3H]mepyramine to monkey brain and have shown that the distribution is similar to that in man, with specific binding sites being concentrated in the frontal cortex with relatively low binding to the pons and basal ganglia. The binding shows a single saturable component with aKDof about 1 nMand a Hill plot slope close to unity. These observations are the same for all structures tested. Comparison with data from other laboratories suggests that in this species, the histamine receptor is the same as that in peripheral tissues. FromKivalues for various ligands and comparison ofKDestimates in other species, the receptor seems to be essentially identical to the H1receptor in central and peripheral tissues of the guinea pig and also to that in human brain. The rat and possibly the dog have minor differences from the monkey in terms ofKDvalues for [3H]mepyramine binding.

ISSN:0008-4212    

DOI:10.1139/y85-125

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The effects of sodium cromoglycate (SCG) on cardiovascular and pulmonary responses to phenylbiguanide, capsaicin, and vagal stimulation were studied in anesthetized guinea pigs. Phenylbiguanide had no bronchospastic activity but induced reflex changes in arterial blood pressure which were reduced or abolished by SCG. Capsaicin induced nonreflex bronchospasm, and decreases in arterial blood pressure that were unaffected by SCG. Sodium cromoglycate, given before or after atropine, had no effect on the bronchospasm and cardiovascular responses to unilateral or bilateral stimulation of the vagus nerves. We conclude that SCG may influence both the afferent and efferent pathways of responses to drugs.

ISSN:0008-4212    

DOI:10.1139/y85-126

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

A method using capillary gas chromatography is described for the determination of histamine and eight of its basic and acid metabolites in a single biological sample of serum, urine, or gastric juice. Ion-exchange chromatography and extraction with organic solvents are used for isolation and purification, and gas chromatography for identification and quantitation. The heptafluorobutyryl derivatives of histamine and some basic metabolites are compatible with nitrogen–phosphorus and electron capture detection modes and offer an excellent sensitivity (detection limit 0.1 pmol with electron capture). The acid metabolites are quantitated after esterification. The linearity range, the sensitivity, a partial study of reproducibility and typical chromatograms show that the method is adaptable to a variety of applications.

ISSN:0008-4212    

DOI:10.1139/y85-127

出版商:NRC Research Press    

年代:1985

数据来源: NRC