Effects of methylnaltrexone on morphine-induced cough suppression in guinea pigs

We administered methylnaltrexone, a peripheral opioid receptor antagonist, to guinea pigs previously injected with morphine sulfate to determine whether the compound could block opioid-induced cough suppression without blocking antinociception. The effects of methylnaltrexone (2.0, 1.6, 0.8 mg/kg) and of naltrexone (0.32, 0.16, 0.02 and 0.01 mg/kg) were compared in animals who had been injected with morphine sulfate (8.1 mg/kg). At 2.0 mg/kg methylnaltrexone, number of coughs returned to baseline value and nociception remained unaffected. At the two higher doses of naltrexone (0.32 and 0.16 mg/kg), morphine-induced antitussive effect was blocked, but antinociception was reversed. Our results suggested that methylnaltrexone possesses opioid antagonist activity in receptors peripheral to the blood-brain barrier. Its peripheral activity makes methylnaltrexone a clinically interesting agent for maintaining the cough reflex in those who must take opioids for analgesia.     

Effects of methylprednisolone pulses on renal function of guinea pigs

Methylprednisolone produced a dose dependant significant increase in glomerular filtration rate, a significant decrease in sodium excretion, and a significant increase in urinary alkaline phosphatase activity in guinea pigs. The renal histology in groups with 4, 5 and 6 doses revealed mild degenerative changes in the tubular epithelial cells. The results suggest the beneficial effects of methylprednisolone pulse therapy on renal function mainly by increasing glomerular filtration rate with only minimal side effects.     

Effects of the respiratory epithelium on the tracheal smooth muscle in guinea pigs]

We studied the influence of respiratory epithelium on tracheal smooth muscle tone of guinea pigs. Mechanical removal of the epithelium induced an increase of the contractile response to histamine. In preparation of smooth muscle previously contracted by histamine, isoproterenol induced dose--dependent relaxation, the level of which was significantly greater in tracheal smooth muscle with epithelium than without it. These results suggest an important role of respiratory epithelium on the contractile activity of smooth muscle.     

Effects of intravenous injection of butyrate on the exocrine pancreatic secretion in guinea pigs

1. The stimulus-secretion coupling in the pancreatic exocrine responses to i.v. injection of sodium butyrate was investigated in guinea pigs in vivo and in vitro. 2. Intravenous single injection of sodium butyrate (12.5-100 mumol/100 g body wt) caused an increase in fluid and amylase secretion in a dose-dependent manner. The responses evoked by sodium butyrate (100 mumol/100 g body wt) were not affected by prior injection of atropine (0.14 mumol/100 g body wt) or hexamethonium (4 mumol/100 g body wt). 3. The chloride concentration in secreted fluid increased slightly with an increase in flow rate in response to sodium butyrate, but decreased in response to secretin. 4. The amylase release from the pancreatic segments evoked by sodium butyrate (10(-6)-10(-2) M) increased dose-dependently. The responses were potentiated in the presence of secretin (1 C.H.R.u./ml), but were suppressed in the presence of acetylcholine (10(-6) M) or in a Ca-free solution containing EGTA (10(-4) M). 5. These results suggest that the secretory effects in response to i.v. injection of sodium butyrate probably arise from direct action on the acinar cells, and that an increase in cellular calcium concentration might be an important step in the secretion process, in guinea pig exocrine pancreas.     

Effects of antiprogesterones on myometrial cell-to-cell coupling in pregnant guinea pigs.

We used intracellular microelectrodes to investigate the effects of the antiprogesterone (AP) compounds RU 486 and ZK 299 on cell-to-cell coupling in the guinea pig myometrium during pregnancy. The input resistance (Ro) of myometrial cells was high in nonpregnant tissues (44.6 +/- 6.39 M omega), but decreased by midgestation (Day 44 or 45 of gestation; 22.9 +/- 3.17 M omega), and was lowest at term (between 17.7 +/- 2.90 m omega and 13.1 +/- 4.34 M omega on Days 59-69). Treatment with the AP RU 486 or ZK 299 in three groups of midgestational animals reduced Ro to a similar level within 24 h. Lucifer Yellow (LY) was injected into smooth muscle cells as a direct but qualitative measure of metabolic coupling. In term and AP-treated animals, LY spread rapidly to neighboring cells within 60 sec, but little spread occurred in midgestational control tissues and no spread was seen even after 10 min in nonpregnant tissues. This correlation of decreased Ro (implying increased electrical coupling) with the development of extensive spread of LY indicates increased electrical and metabolical coupling between myometrial cells during labor. These data show that myometrial smooth muscle cells of guinea pigs are moderately well coupled before the onset of labor, and the coupling increases further, just prior to spontaneous delivery or due to treatment with APs. These events may be required for synchronizing and coordinating the electrical, metabolic, and contractile activity of labor.     

Effects of nicardipine on the spontaneous beat of isolated atria of guinea pigs

Nicardipine was found to produce a concentration-dependent depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. It also depressed the atrial rate of the isolated, spontaneously beating atria of the guinea-pig. The effect of the increasing concentrations of nicardipine on the heart rate was negligibly weaker than its effect on the isometric contraction. A time-dependent depression of the isometric contraction and the atrial rate after the addition of a single dose of nicardipine was also found up to the 10th min. Calcium almost completely, isoprenaline completely and aminophylline partially antagonized the depressive action of nicardipine on the isometric contractility of the atria. Only isoprenaline antagonized the negative chronotropic action of higher doses of nicardipine. It is possible that these substances restore the contractility by compensating the calcium balance, previously changed by nicardipine, or by producing an increase in the intracellular cAMP content (isoprenaline and aminophylline).