摘要:

The selectivity of coupling of m1, m3, and m5 muscarinic receptors to activation of the neuronal type of nitric oxide synthase was investigated. Stimulation with the agonist carbachol of all three receptor subtypes expressed in Chinese hamster ovary cells resulted in a rapid and transient activation of the enzyme, as measured by stimulation of guanylate cyclase in reporter neuroblastoma cells. Carbachol was more potent and efficacious at m5 receptors than at the other two receptor subtypes. Stimulation of all three muscarinic receptors resulted in an increased concentration of intracellular calcium, with a time course that preceded activation of nitric oxide synthase. At each receptor subtype, there was a close relationship between the magnitude of the maximal calcium response and that of enzyme activation.

ISSN:0031-7012    

DOI:10.1159/000139439

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an α1-adrenergic receptor antagonist) and yohimbine (an α2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of α1-adrenoceptors and that inhibitory effects require α2A-adrenocept

ISSN:0031-7012    

DOI:10.1159/000139440

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of optical isomers of ephedrine and methylephedrine on the guinea pig tracheal smooth muscle were studied. l-Ephedrine markedly caused a graded relaxation of the guinea pig trachea where the tone had been raised spontaneously. A rightward shift of the l-ephedrine concentration-response curve was observed for propranolol and butoxamine, and the PA2 values for propranolol and butoxamine were 8.55 and 6.38, respectively. d-Methylephedrine markedly caused a graded relaxation of the guinea pig trachea contracted with histamine. Propranolol and bupranolol did not affect the relaxant response to d-methylephedrine. d-Methylephedrine competitively antagonized the contractile responses to histamine, and the pA2 value for d-methylephedrine was 5.12. These results suggest that l-ephedrine-induced relaxation of the guinea pig trachea is mediated through β2-adrenoceptors, whereas d-methylephedrine relaxes the guinea pig trachea by blocking histamine receptors

ISSN:0031-7012    

DOI:10.1159/000139441

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of phosphodiesterase inhibitors, an activator and an inhibitor of guanylyl cyclase, and cAMP and cGMP analogs on oxytocin-induced contractions have been studied in the testicular capsule of rats. The nonspecific phosphodiesterase inhibitors, theophylline and caffeine, attenuated the oxytocin-induced contractions via mechanisms that seem to be related to an increase in cAMP levels, since a similar effect was produced by dibutyryl cAMP. Sodium nitroprusside facilitated oxytocin-induced contractions. This effect was mimicked by dibutyryl cGMP. Methylene blue, an inhibitor of soluble guanylyl cyclase, decreased oxytocin-induced contractions, which suggests an involvement of guanylyl cyclase in the oxytocin effect. These results suggest that cAMP modulates the contraction and that cGMP, contrary to what happens in most smooth muscles, could participate in oxytocin-induced contractions in the testicular capsule of rats.

ISSN:0031-7012    

DOI:10.1159/000139442

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of nipradilol, an ocular hypotensive drug, on isolated canine retinal central arteries and on retinal arterioles in vivo were investigated. Nipradilol (10–9 to 10–5 mol/l) produced a dose-related relaxation of the arterial strips contracted with prostaglandin F2α which was not influenced by timolol or indometacin. The median effective concentration of this drug was five times that of glycerol trinitrate (GTN). The nipradilol-induced relaxation in the endothelium-intact strips was not influenced by NG-nitro-L-arginine, a nitric oxide synthase inhibitor, but was abolished by oxyhemoglobin and methylene blue. Treatment with high concentrations of sodium nitroprusside abolished the response to nipradilol, as observed with that to GTN. Retinal arterial strips responded to isoproterenol with a slight relaxation which was depressed by nipradilol. In anesthetized dogs, intra-arterial injections of nipradilol dilated the retinal arterioles in the ocular fundus; the dilator potency was approximately one fifth that of GTN. It is concluded that nipradilol dilates canine retinal arteries in vitro and arterioles in vivo, possibly due to activation of soluble guanylate cyclase and increased production of cyclic guanosine monophosphate that are associated with nitric oxide liberated from the molecule itself in the tissue but not derived from the endothelium and perivascular nerve. Beta adrenoceptor blocking action was determined in the retinal ar

ISSN:0031-7012    

DOI:10.1159/000139443

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In isolated perfused rat hearts with coronary occlusion and reperfusion, the effect of adenosine antagonists on the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated. An antagonist with high selectivity for the A⇓ receptor, 8-phenyltheophylline, was applied and compared with the relatively unspecific antagonist theophylline, used in its water-soluble form aminophylline. Depending on the duration of coronary occlusion, more or less severe tachyarrhythmias occurred during the myocardial ischemia, and particularly during the subsequent coronary reperfusion. Large amounts of the nucleosides and oxypurines were released after reopening the coronary artery. The release was particularly high in hearts with ventricular fibrillation. Both adenosine antagonists increased the release in a highly significant way. The findings let assume that adenosine has perhaps a modulating effect on its own release, which can be blocked by adenosine antagonist

ISSN:0031-7012    

DOI:10.1159/000139444

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Urinary bladder smooth muscle contraction can be evaluated using field stimulation (neurohumoral transmission), carbachol (muscarinic stimulation), and KCl (direct membrane depolarization). We recently evaluated the activity of a novel organic chemical, macrocycle-1 on the contractile responses of the bladder to field stimulation, carbachol, and KCl. Isolated strips of rabbit bladder were mounted in individual baths containing 7.5 ml Tyrode’s solution. The response to FS (1-32 Hz), carbachol (1 µmol/l), and KCl (120 mmol/l) were determined in the presence and absence of 3 different concentrations of macrocycle-1. Maximal tension, the rate of tension generation, the time to maximal tension, and the rate of decay following maximal tension were determined. The results can be summarized as follows: (1) In the absence of macrocycle-1, maximal tension and the maximal and mean rate of tension generation increased with frequency, whereas the time to maximal tension was constant. The rate of decay of tension following maximum tension was greater for 8, 16 and 32 Hz as compared to 1 or 2 Hz. (2) The maximal response to KCl was lower than either FS or carbachol. The maximal rates of tension generation for carbachol and KCl were lower than that of FS; and the rate of tension generation for KCl was lower than that of carbachol. The time to maximal stimulation for KCl was greater than that of either carbachol or FS. (3) Macrocycle-1 had a greater inhibitory effect on KCl stimulation than on carbachol stimulation; and a greater inhibitory effect on KCl and carbachol stimulation than on FS. (4) The rate of tension generation was more sensitive to macrocycle-1 inhibition than was the maximal tension responses to all methods of stimulation. Our current hypothesis is that macrocycle-1 is acting as an intracellular calcium buffer whose affinity constant and association rate does not interfere with rapid intracellular release mechanisms (FS) while it inhibits slow intracellular calcium release mechanisms (carbachol and KC

ISSN:0031-7012    

DOI:10.1159/000139445

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We observed the effect of the 5-hydroxytryptamine synthesis inhibitor p-chlorophenylalanine on aggression in male firemouth cichlids (Cichlasoma meeki). p-Chlorophenylalanine-treated firemouths showed a significantly greater number of mirror-directed bites as compared with saline-injected controls. This finding is consistent with the effects of this drug on social aggression in mammals and birds and supplements previous reports that 5-hydroxytryptamine inhibits aggression in fish.

ISSN:0031-7012    

DOI:10.1159/000139446

出版商:S. Karger AG    

年代:1996

数据来源: Karger