No abstract

The effects have been investigated of the regulatory peptides, substance P (SP) and bombesin, on the secretion of [14C]glucosamine-labeled trichloroacetic acid-phosphotungstic acid precipitable glycoproteins by canine tracheal explants. SP (10(10) to 10(-7) M) induced a dose-dependent increase in secretion of high-molecular-weight (greater than 2 X 10(6) radiolabeled glycoproteins predominantly from the submucosal glands. On a molar basis, SP [median effective concentration (EC50) = 8.2 X 10(-10) M] was about 1,000-fold more potent than methacholine (EC50 = 6.3 X 10(-7) M). Bombesin (10(-10) to 10(-4) M) had no effect on glycoprotein secretion. The time course of SP effect was characterized by an initial stimulation of glycoprotein secretion followed by a period of inhibition, suggesting that it rapidly exhausts a pool of glycoprotein, possibly that present within the duct lumen of the submucosal gland. Consistent with this are the findings that SP-induced secretion of glycoprotein was augmented by preincubation with methacholine while methacholine-induced secretion was diminished by preincubation with SP. Our findings show that SP is a potent stimulant of airway glycoprotein secretion in vitro and suggest that it acts by increasing the rate of clearance of mucus from the ducts of the submucosal gland, possibly by induced constriction of the secretory tubules and collecting duct. A role is discussed for SP in mucus hypersecretion induced by local axonal reflexes in the airway mucosa.

Summary: This study compared the ability of three N methyl-D-aspartate (NMDA) receptor antagonists to pre vent neuronal degeneration in an animal model of global cerebral ischemia. The model employed is characterized by damage to the striatum, hippocampus, and neocortex. Antagonists were administered to gerbils either before or after a 5-min bilateral carotid occlusion. The intrais chemic rectal temperature was either maintained at 36--37°C or allowed to fall passively to 28-32°C. Antago nists and doses tested were I and 10 mg/kg of MK-801 (pre-or postischemia), 30 mg/kg of COS 19755 preis chemia, four 25 mg/kg doses of COS 19755 administered between 0.5 and 6.5 h postischemia, and 40 mg/kg of MDL 27,266 (pre-or postischemia). All three NMDA re ceptor antagonists exhibited some degree of neuroprotec tive activity when the carotid occlusion was performed under normothermic conditions. Most of the treatments with antagonist markedly reduced striatal damage. CAl hippocampal and neocortical pyramidal cells were spared