Acta physiologica et pharmacologica Bulgarica最新文献

Electrical field stimulation (EFS) elicited two types of responses from longitudinal muscle strips of the distal cat ileum: contraction at switching on the stimulation (in 62% of the strips) and inhibition of the phasic contractions at switching on the stimulation followed by contraction in 38% of the strips. In all strips the muscarinic acetylcholine subtype M1-receptor agonist (4-Hydroxy-2-butynyl)-1-trimethylammonium-m-chlorocarbanilate chloride (McN-A-343) increased the tone and amplitude of the spontaneous contractions. On this background EFS elicited an inhibition of the phasic contractions at switching on the stimulation followed by contraction. Blockade of nitric oxide (NO)-synthase by Nw-nitro-L-arginine (L-NNA) transformed the inhibitory response into contraction and this transformation was partly overcome by L-arginine. The results suggest that presynaptically situated M1 receptors are involved in the NO pathway.

The effects of bombesin (BM) on the canine gallbladder motility was studied under two different experimental conditions: (i) in conscious dogs with a balloon chronically implanted into the gallbladder lumen where intragallbladder pressure was recorded in mm Hg by means of a pressure transducer, and (ii) in smooth muscle preparations isolated from different regions of the gallbladder where the contractions were recorded isometrically by means of mechanoelectrical transducers. Similar to CCK8 bolus injection of. BM i.v. increased the gallbladder pressure in a dose-dependent manner. The response was characterized by a slow increase of the tone and a gradual restoration (in 4 to 8 min) of the background activity. The threshold dose and the maximum dose were 30 ng/kg and 100 ng/kg for BM and 1 ng/kg and 10 ng/kg for CCK8, respectively. Both atropin (10 to 50 micrograms/kg) and hexamethonium (0.5 to 3 mg/kg) injected i.v. 5 to 10 min before BM strongly reduced or even abolished the gallbladder response to BM. Somatostatin (1 to 2 micrograms/kg) and VIP (0.5 to 1 microgram/kg) injected 3 to 5 min before BM also exerted a strong inhibitory effect on the canine gallbladder response to BM. However BM (up to 10(-6) M) had no effect on the spontaneous or electrically-induced contractions of the canine gallbladder smooth muscle preparations. The results suggest the involvement of prejunctional cholinergic-, somatostatinergic- and VIP-ergic pathways in the bombesin-induced increase of the gallbladder pressure of conscious dogs.

The differentiation of the argyrophil, argentaffin, 5-hydroxytryptamine (5-HT)-, somatostatin (SOM)-, cholecystokinin (CCK)-, substance P (SP)-, methionine-enkephalin (Met-Enk)- and vasoactive intestinal polypeptide (VIP)-immunoreactive entero-endocrine cells (EECs) was examined in human fetuses. A great increase in the frequency of EECs in the duodenum and the rectum was observed between the 7th and 12th gestation week. The differentiation of the EECs advanced distally in the small intestine and proximally in the large intestine. In 24-25-week-old fetuses the frequency of the EECs was also increased in the ileum and the colon. A different time-course of the appearance and differentiation of the types of EECs was observed. Met-Enk- and VIP-immunoreactive endocrine cells were not detected at any age. A regional difference in the frequency and morphology of the endocrine cell types was observed in the eldest fetuses.

The neuropeptides of the cholecystokinin (CCK) group belong to the substances usually referred to as "brain-gut" neuropeptides. They are synthesized in neurons of the central nervous system, in the peripheral and in the autonomous nervous systems, in endocrine cells (types "I", "K" and "A"), as well as in the enteric nervous system of the gastro-intestinal tract and of the pancreas. The CCK-group peptides realize their effects via several different mechanisms (Fig. 1): endocrine or neuroendocrine (classic hormonal mechanism)--the peptide, released by the endocrine cell or by the nerve terminal, is carried by the circulation to the remote target organs; paracrine or neuroparacrine--the peptide, released in the intercellular space, reaches the target effector cells via diffusion. Similarly to the classic neurotransmitters, CCK and its analogues could play a neurotransmitter role, also modulating the release of acetylcholine (ACh) and of other neurotransmitters in enteric and CNS neurons. In the present review article some smooth-muscle and neuromodulatory effects of CCK are described and compared to the results of the authors' studies on the problem.

Behavioral and nociceptive effects of dotarizine (DOT) and other substances acting on migrainous attacks and nitric oxide (NO) metabolism were studied in comparative experiments on rats. Behavioral effects were evaluated by the changes induced in ambulations and rearings of rats in the Opto-Varimex apparatus; effects on nociception were determined by the changes of pain threshold in growing mechanical pressure on one of the rat paw. The data showed that (1) NO did not participate directly in the mechanism of the behavioral actions of DOT. A role could be ascribed to the modulating influence of DOT on the changes in NO formation induced by other agents; (2) the NO system did not participate in the mechanisms of the responses to the painful mechanical pressure on the rat paw; (3) the behavioral effects of the substances with facilitating or inhibitory action on the migrainous process (m-CPP and ergotamine) and the influence of substances proved to affect NO formation (L-arginine, histamine, L-NAME) on these effects suggest a role for NO as a modulating but not a basic factor in the mechanisms of action of these pro- and antimigrainous substances; and (4) the behavioral effects of DOT were similar to the effects of the antimigrainous drug ergotamine and different from the promigrainous drug meta-chlorophenyl-piperazine (m-CPP)--which suggest an antimigrainous activity of dotarizine.

The paper describes an apparatus constructed by the authors and aimed at evaluating the optical density of human ocular media by a non-invasive psychophysical method described previously (Sample et al. 1988). The device has two light sources within the wavelength bands of 437 +/- 6 nm and 557 +/- 6 nm, respectively. They are a square-wave alternated at 1 Hz. The radiance of each can be controlled by the subject and adjusted at visibility threshold or at subjective equiluminance. Upon scotopic vision, the ratio between the two thresholds (or ratio of radiances at equiluminance) is a function of the ocular optical density at the short wavelength. The psychophysical procedures of adjustment of the 437 nm source at the absolute threshold and at equality with the 557 nm source had been tested with volunteers aged between 24 and 67 years. The dependence of blue-light sensitivities on age, obtained with the two procedures, suggests, in agreement with the literature, two main sources of sensitivity decline with age: senile myosis and ocular-media density increase at the short wavelength end of the visible spectrum.

In order to study the contribution of eicosanoids to the regulation of the functions of normal and carbon tetrachloride (CCl4)-injured liver cells, primary cultures of hepatocytes (HC) either alone or in coculture with Kupffer cells (KC) were exposed for 4 and 24 h to lipoxygenase inhibitor (nordihydroguaiaretic acid-NDGA) or cyclooxygenase inhibitor (indomethacin-IND) in the presence and in the absence of CCl4. Treatment with CCl4 resulted in increased ALT release and a decreased mitochondrial respiration (MR) in HC and their cocultures with KC. The addition of NDGA decreased ALT levels and increased MR in control and CCL4-injured cells. Urea production (UP) was not significantly affected by NDGA. In contrast, addition of IND) decreased UP by HC (4 h), and did not alter ALT release and MR in control and CCl4-treated cells. These results indicate that arachidonic acid metabolites are involved in the regulation of HC flinctions. There is also evidence that a protective action of lipoxygenase inhibitors on CCl4-injured liver is mediated, at least partly, by their direct effects on HC and KC, in particular by increasing the mitochondrial respiration.

In this work we tried to perform a dynamic analysis of coronary vascular response to histamine, using a simple mathematical analysis as a first step in the better understanding of complex histamine effects on coronary blood vessels of the isolated guinea pig heart. So, we defined more parameters, such as: I and delta I to quantify the intensity of coronary perfusion pressure (CPP) change, T and dt to quantify the time CPP change occurs and D to characterize the intensity and duration of CPP change, i.e. to quantify the dynamics of this change.

The aim of this study was to evaluate the participation of the suprachiasmatic nuclei (SCN) in the generation and synchronization of cardiovascular rhythms. Seven sham-operated and 11 SCN-lesioned animals maintained under 12/12 hr light/dark cycle were used. Systolic arterial pressure (SAP) and heart rate (HR) were measured indirectly during 24-hour periods at 3-4 hour intervals. The data were analyzed using individual and group cosinor rhythmometry and Fourier analysis. A circadian rhythm of water intake was not detected in animals with successful SCN lesions. A reduction of the double amplitude/MESOR ratio for the 24-hour component of drinking rhythm in the SCN-lesioned rats was observed. After SCN lesions the group 24-hour rhythm of SAP was eliminated while a significant group circadian rhythm for HR was detected. The individual amplitude/MESOR ratios for the 24-, 12-, 8- and 6-hour periodic components of SAP and HR in the lesioned rats showed no marked differences as compared with controls. The generation and entrainment of circadian variations in HR is probably not dependent on the integrity of SCN in rats. The SCN may participate in the entrainment of the circadian rhythm of SAP. The combination of completely abolished (water intake) and persisting (heart rate) rhythms further supports that the circadian regulatory system consists of a network of multiple oscillators.

The effects of angiotensin II (ATII) administered intracerebroventricularly (i.c.v.) at a dose of 0.5 microgram per mouse on the activity of monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in the forebrain of normoxic and hypoxic mice were studied. The influence of hypoxia (asphyctic and haemic) on MAO-A and MAO-B activity was also investigated. MAO-A activity was increased in haemic hypoxia; MAO-B activity increased in both asphyctic and haemic hypoxia. ATII increased MAO-A activity without affecting MAO-B activity under normoxic conditions. ATII increased MAO-A activity but decreased MAO-B in hypoxic (asphyctic) mice as compared to normoxic controls. The results suggest the role of MAO-A and MAO-B in the ATII-induced increase of susceptibility to acute hypoxia.