ISSN:0031-7012    

DOI:10.1159/000138498

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The purpose of this review is to examine the role of vagal influence on the regulation of gastric acid secretion in humans, and to answer the question as to whether there is any indication of increased vagal tonus being involved in the pathogenesis of peptic ulcers. Apart from the central importance of vagal influence on gastric acid secretion, there is no direct evidence for the existence of general vagal hyperactivity in peptic ulcer patients. Increased vagal activity can only be indirectly demonstrated for a subgroup of duodenal ulcer patients. The involvement of psychodynamic factors as a background phenomenon is emphasized.

ISSN:0031-7012    

DOI:10.1159/000138499

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Male Sprague-Dawley rats maintained under controlled environmental conditions were used. Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were determined in the cerebral cortex, bulbus olfactorius, midbrain, hypothalamus, hippocampus, cerebellum, pons and medulla oblongata of control rats and rats treated with apomorphine (15 mg/kg, i.p.) after a single dose or after a second dose administered 24 h later at 10.00 or 22.00 h. Results of this experiment indicate that the repeated administration of apomorphine at 10.00 h was associated with rapid development of tolerance to the hypothermic action of this drug. A single injection of apomorphine resulted in significant (p < 0.01) decrease of AChE and significant increase of ChAT activity (p < 0.01) in the cortex, hypothalamus and pons. There were no significant differences between tolerant and control animals in the activities of AChE or ChAT in the bulbus olfactorius, cerebral cortex, midbrain, pons or medulla. On the other hand, repeated administration of apomorphine at 22.00 h was not associated with tolerance to the hypothermic action of this drug. A single injection of apomorphine at 22.00 h resulted in significant (p < 0.01) increase in AChE activity of the midbrain, hippocampus, and the medulla oblongata with no significant changes in the cerebral cortex and bulbus olfactorius. There was a significant decline (p < 0.01) of ChAT activity of the hypothalamus, hippocampus, cerebral cortex and the medulla oblongata (p < 0.05). Meanwhile, there was a significant (p < 0.05) increase of ChAT activity of the midbrain with no significant changes in the cerebellum, pons and the bulbus olfactorius. These findings indicate that changes in the responsiveness of the brain cholinergic enzymes following repeated administration of apomorphine may explain the increase in hypothermia during the dark phase and the rapid development of tolerance during the light phase.

ISSN:0031-7012    

DOI:10.1159/000138408

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The facilitatory actions of muscarine on synaptic transmission were measured in rat superior cervical ganglia in vitro. Muscarine (300 nmol/l) induced increases in sub-maximal population action potentials, which were mimicked by the Ml receptor agonist McN-A-343 (1 μmol/l) and antagonized by the Ml receptor antagonist pirenzepine (100 nmol/l) and telenzepine (100 nmol/l), but not by the M2 receptor antagonist AF-DX 116 (1 μmol/l). Slow excitatory postsynaptic potentials recorded from curarized rabbit isolated superior cervical ganglia were also blocked by telenzepine (300 nmol/l) but not by AF-DX 116 (3 μmol/l). It is concluded that Ml receptors mediate the excitatory actions of muscarinic agonists in these sympathetic gangl

ISSN:0031-7012    

DOI:10.1159/000138501

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Rats with portacaval shunt, although showing no changes in their spontaneous pain threshold, did display an increased sensitivity of analgesic responses to morphine injection. In addition, these portacaval-shunted animals had a lower level of spontaneous motor activity and a reduced sensitivity of locomotor stimulant responses to amphetamine administration. However, these portacaval-shunted animals displayed same thermoregulatory responses to various ambient temperatures as those of normal unoperated or sham-operated animals. Biochemical examination revealed that these portacaval-shunted animals had a higher indoleamine synthesis in both the hypothalamus and the brain stem, but had a lower catecholamine synthesis in both the hypothalamus and the corpus striatum. The data suggest that alterations in antinociceptive and locomotor stimulant responses of the portacaval-shunted animals correlate with patterns of monoamine synthesis in different brain regions (patterns that differed from those observed in normal unoperated animals or in sham-operated animals).

ISSN:0031-7012    

DOI:10.1159/000138409

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Stimulation of acid secretion by muscarinic agents involves receptors with a higher apparent affinity to the M1-antagonists, pirenzepine and telenzepine, than those regulating heart rate and salivary secretion. However, the localization of the proposed M1-receptors regulating acid secretion remains unclear. Studies with parietal cells isolated from several species indicate that parietal cells have a muscarinic receptor with low affinity for the M1-antagonists. Our studies with somatostatin cells isolated from canine fundic mucosa indicates that the muscarinic receptor inhibiting somatostatin release also is of low affinity for M1-antagonists. We have found no evidence for regulation of histamine release from canine fundic mast cells, whereas there is evidence that acetylcholine induces histamine release from the enterochromaffin-like cells of the rat and rabbit fundic mucosa. Further studies will be necessary to determine which of the muscarinic receptors potentially involved in the regulation of acid secretion is responsible for the M1-behavior of this pathway.

ISSN:0031-7012    

DOI:10.1159/000138502

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Receptors may be grouped into superfamilies, according to their mechanism. Muscarinic receptors belong to one such superfamily, that of the G-protein coupled receptors. Subtypes of muscarinic receptors may be defined according to their primary amino acid sequence, their mechanism and their pharmacology. However, there is as yet no consistent scheme to explain the pharmacology and function of each molecular subtype. The pharmacological tools which distinguish between muscarinic receptor subtypes are described and the emerging evidence for the location of the ligand binding site is discussed.

ISSN:0031-7012    

DOI:10.1159/000138503

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

We reported that verapamil, nicardipine and diltiazem inhibited both 3H overflow and contraction induced by transmural nerve stimulation (TNS) in the canine saphenous vein preloaded with 3H-noradrenaline. In the present study, the effects of these Ca channel antagonists in the presence of tetraethylammonium (TEA) were investigated to evaluate whether the antagonists act by inhibiting Ca2+ influx into the nerve endings. The effects of the drugs on both responses to tyramine were also studied. In the 1 mmol/l-TEA-pretreated veins, verapamil and nicardipine inhibited only the contraction. Diltiazem inhibited the two parameters, the effects being nearly equipotent to those in the absence of TEA. The L-cis isomer of diltiazem inhibited the TNS-evoked responses to a similar degree as diltiazem, which was unaffected by 1 mmol/l TEA. Verapamil, nicardipine and diltiazem inhibited the TNS-evoked 3H overflow in 0.25 mmol/l Ca2+ and 20 mmol/l TEA medium, the inhibitions by the two former antagonists being greater than those seen in normal Krebs solution. TEA (1 mmol/l) added after the Ca channel antagonists, overcame the inhibition of the evoked overflow by diltiazem more poorly than that by verapamil or nicardipine. Only verapamil inhibited both responses to tyramine. These data together with previous results suggest that unlike verapamil and nicardipine, diltiazem may inhibit the TNS-evoked neu-rotransmitter release via a mechanism being unrelated to its Ca2+ influx-inhibiting action, resulting in an inhibition of the contraction, and that only verapamil inhibits the tyramine-evoked neurotransmitter release.

ISSN:0031-7012    

DOI:10.1159/000138410

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The affinities of telenzepine, pirenzepine and atropine for muscarinic acetylcholine receptors have been determined by receptor binding studies using brain cortex and heart membranes of calf and rat. The ratios of affinities of telenzepine and pirenzepine for the cortical M1 receptors, cortical ‘non-M1’ receptors and cardiac M2 receptors are 50:5:1 and 80:5:i, respectively. The time course of association of telenzepine and pirenzepine with M1 receptors is similar, whereas the half-times for dissociation are 35 and 2.3 min at 37 °C, respectively. In further experiments this slow dissociation rate of telenzepine is shown to be rate-limiting for the occupation of M1 receptors by other ligands. The prolonged occupation of M1 receptors by telenzepine is discussed as a possible protective mechanism against acetylcholine released from vagal nerve fi

ISSN:0031-7012    

DOI:10.1159/000138504

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The purpose of the present investigation was to compare the effects of some phenylalkylamine calcium entry blockers on postischemic energy metabolism in the isolated perfused rat brain. To differentiate between calcium entry blockade and nonspecific effects the optically active stereoisomers of emopamil were investigated. At a concentration of 10 μmol/l both gallopamil and emopamil enhanced the postischemic restoration of high-energy phosphate levels. The racemic mixture and the (–)-enan of emopamil and noremopamil caused similar metabolic changes at 1 μmol/l. The (+)-enantiomer of emopamil proved to be ineffective at either 1 or 10 μmol/l. The effects on energy metabolism were accompanied by an increase in the postischemic perfusion rate. The results suggest that the drug efficacy necessary to accelerate the restitution of postischemic energy metabolism is in the order of noremopamil > emopamil > gallopamil. The effects of the phenylalkylamine calcium entry blockers on energy metabolism are discussed in relation to vasodilation due to calcium entry bloc

ISSN:0031-7012    

DOI:10.1159/000138411

出版商:S. Karger AG    

年代:1988

数据来源: Karger