General pharmacology最新文献

1. The effects of three class I antiarrhythmic drugs quinidine, lidocaine and lorcainide on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase, EC 3.6.1.3] activity were evaluated in guinea pig heart preparations. 2. All three drugs inhibited the enzyme activity in a concentration-dependent fashion. 3. Lorcainide was the most potent, exerting inhibitory effects in the range of less than 1.0 nM-2.0 mM, with IC20 and IC50 values of 9.4 +/- 0.6 nM and 87.2 +/- 5.5 microM. However, in the range of approx. 10 nM-10 microM, the enzyme response decreased only slightly with increasing lorcainide concentrations. 4. Quinidine and lidocaine, on the other hand, inhibited the enzyme activity in the range of 1.0 microM-100 mM. 5. The IC20 and IC50 values for quinidine were 0.92 +/- 0.04 mM and 4.8 +/- 0.6 mM and for lidocaine were 115 +/- 6 microM and 2.3 +/- 0.3 mM. 6. The results show that all three drugs inhibit mitochondrial ATPase activity and that lorcainide is the most potent. 7. These inhibitory effects may be related to the lipophilicity and membrane stabilizing activity of this class of antiarrhythmic drugs.

1. Sulphated cholecystokinin octapeptide (CCK8S, 0.03-1.00 microM), pentapeptide (CCK5) and tetrapeptide (CCK4) elicited concentration dependent depolarizations of neonate rat ventral roots in vitro. 2. CCK5 was equipotent with CCK8S although CCK4 was weaker (equipotent molar ratio 17.5). 3. CCK8S-induced depolarizations were depressed by tetrodotoxin (0.1 microM), Mg2+ ions (0.75 mM) and the NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5, 10 microM). These results suggest that CCK8S-induced depolarizations were predominantly mediated through the release of an excitatory amino acid from interneuronal sites. 4. The selective CCKA and CCKB receptor antagonists, L-364,718 and L-365,260 both depressed CCK8S-induced depolarizations. CCK8S dose ratios in the presence of 1 microM L-364,718 or L-365,260 were 4.5 and 11.2 respectively, suggesting the response was mediated predominantly through stimulation of CCKB receptors. 5. These results suggest that the neonate rat hemicord preparation is a suitable tissue for functional CCK receptor assays.

1. Neuropeptide Y (NPY) increased inositol phosphate (IP) formation in the femoral artery and vein of adult Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. Noradrenaline (NA, 10(-6) M) induced IP accumulation in both strains of rats. 3. Subthreshold concentrations of NPY (3 x 10(-9) M for femoral vein and 10(-8) M for femoral artery) failed to modify NA (10(-6) M)-induced IP formation in both vessels. 4. These results suggest that the direct contractile effects but not the potentiation of NA-induced contractions may be directly linked to phosphatidylinositol turnover in adult SHR and WKY rats.

1. In this study, we investigated the contractile effects of acetylcholine (ACh) and KCl in tracheas obtained from 12-13 wk insulin-dependent (ID)-diabetic rats. 2. The maximum contractile responses to ACh and KCl were significantly increased in ID-diabetic rat tracheas compared with those from controls. But the sensitivity (pD2 values) of ID-diabetic tracheas to these agents were not significantly altered relative to controls. 3. The alterations which occurred in ID-diabetic rats were prevented with oral vanadyl treatment during a 10 wk period.

1. Permanently charged AZA analogs of chlorpromazine inhibited the binding of [3H]spiperone and antagonized the apomorphine-induced inhibition of the potassium evoked release of [3H]acetylcholine. 2. The AZA analogs were more potent in binding affinity and antagonist activity than the trimethylammonium analog of chlorpromazine but less potent than chlorpromazine. 3. These results suggest that it is possible to enhance the binding of the permanently charged trimethylammonium analog of chlorpromazine by the addition of a functional group near the quaternary nitrogen which is capable of forming a hydrogen bond with the D2 dopamine receptor. 4. However, it appears that for optimal binding, as achieved with chlorpromazine, the hydrogen-bonding proton should be on the charged nitrogen.

1. Hemodynamic effects of physiological (0.04 and 0.07 mM) and high (8, 15 and 25 mM) L-carnitine (LC) concentrations were tested on the normally oxygenated and hypoxic perfused rat heart. 2. No effect was detected on aerobic hearts, whereas a dose-dependent rise in coronary flow (CF) during both the hyperemic and constrictive phases was observed in hypoxic hearts with 8, 15 and 25 mM LC. This action was apparently unrelated to a resting tension (RT) improvement, which was observed only with 25 mM LC. 3. When 11 mM glucose was replaced by 11 mM mannitol in the perfusion buffer, LC effects on the hyperemic phase were abolished; however, 25 mM LC resulted in CF-values still significantly higher than those detected without the drug, though RT was similar in these glucose-free groups. 4. It may be concluded that LC is ineffective on the perfused rat heart in aerobic conditions, whereas high LC concentrations can enhance CF only during hypoxia, these effects being independent of heart function improvements and partly unrelated to glucose presence.

1. The effects of beta-adrenoceptor blockade and reserpinization on the positive chronotropic and inotropic responses to lysophosphatidylcholine (LPC) were examined in isolated atrial and ventricular preparations from rat hearts. 2. The positive responses to 10(-4) M LPC were about 40-55% of those to 10(-5) M norepinephrine (NE) in each preparation. 3. The responses to LPC in the presence of propranolol or in the reserpinized preparations were significantly smaller than the corresponding values obtained in control preparations, and were about 10-25% of those to NE. 4. It was concluded that positive chronotropic and inotropic responses to LPC are at least partially mediated by release of NE from myocardial sympathetic nerve terminals.

1. Administration of apomorphine to mice induced straub tail behaviour dose-dependently. The response was decreased by the D1 antagonist SCH 23390, the D2 antagonist sulpiride. Reserpine plus alpha-methyl-p-tyrosine (AMPT), caused a marked increase in the response of the drug. 2. The D1 agonist SKF 38393 induced the straub tail behaviour in a dose-dependent manner, which was decreased by SCH 23390, sulpiride or reserpine + AMPT. 3. When animals were administered the D2 agonist quinpirole, a dose-dependent response was produced. This effect was decreased by sulpiride and reserpine + AMPT, but not by SCH 23390. 4. In animals pretreated with reserpine + AMPT, the combination of SKF 38393 with quinpirole produced a significant straub tail behaviour. 5. It is concluded that the concurrent D1/D2 dopamine receptor stimulation is necessary to produce straub tail behaviour in mice.

1. Effects of alloxan-induced diabetes on the rat gastric acid secretion were investigated using a number of biostatistical models described earlier. 2. Histamine-induced gastric acid secretion was found to be decreased in alloxan-diabetic rats when compared with their age-matched controls. 3. Basal acid secretion was also decreased depending on experimentally-induced diabetes. 4. The above results strongly suggest that alloxan-induced diabetes depresses vagal activity and H2-receptor activity in the stomach.

1. Josamycin concentrations in cyst wall (wall) and cyst fluid (fluid) of radicular cyst and serum following a single oral administration of josamycin (600 mg) were assayed by a paper disk method. 2. The mean peak josamycin concentrations in wall, fluid and serum occurred at 1.5, 2 and 1.5 hr, respectively, and were 1.33 micrograms/g, 0.53 and 0.74 micrograms/ml, respectively. 3. The mean concentration ratios of wall/serum, fluid/serum and fluid/wall at the peak times (1.5, 2 and 2 hr) were 1.80, 0.64 and 0.42, respectively. 4. Josamycin concentrations in wall and fluid at the peak time exceeded MIC for 80% for clinically isolated strains of alpha-hemolytic Streptococci.