Drugs online research references
Otolaryngol Head Neck Surg. 1998 Sep;119(3):278-87.
Nitric oxide is a regulator of mucociliary activity in the upper respiratory tract.
Runer T, Cervin A, Lindberg S, Uddman R.
Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital, Lund, Sweden.
The in vitro effects of the nitric oxide (NO) substrate L-arginine on ciliary beat frequency and the in vivo effects of the NO donor sodium nitroprusside (SNP) on mucociliary activity were investigated in the rabbit maxillary sinus mucosa with photoelectric techniques. L-Arginine increased ciliary beat frequency in vitro with a maximum response of 27.1% +/- 6.4% at 10(-3) mol/L, and this effect was reversibly blocked by pretreatment with the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine, whereas D-arginine had no such effect. SNP increased mucociliary activity in vivo, the peak response of 36.8% +/- 4.2% being obtained at the dose of 30.0 microg/kg. No tachyphylaxis was observed after repeat challenge with SNP. The increase in mucociliary activity caused by SNP was largely unaffected by pretreatment with the calcium channel blocker nifedipine, the cyclooxygenase inhibitor diclofenac, and the cholinergic antagonist atropine. The nonselective beta-blocker propranolol delayed the peak response of SNP to 7 to 8 minutes after challenge, compared with 1 to 2 minutes after challenge in animals without pretreatment. The results show the NO substrate L-arginine and the NO donor SNP to have ciliostimulatory effects in vitro and in vivo, respectively. The occurrence of NOS production in the sphenopalatine ganglion and sinus mucosa of the rabbit was studied by immunohistochemistry for NOS activity or nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry. The latter is an indirect sign of neuronal NOS activity. Numerous NOS-containing cell bodies were seen in the sphenopalatine ganglion; in the sinus mucosa a moderate supply of thin NOS-immunoreactive nerve fibers was seen. Taken together, the morphologic findings and the functional results indicate NO to be a regulator of mucociliary activity in upper airways.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9743084&dopt=Abstract
Am J Physiol. 1993 Oct;265(4 Pt 1):G725-34.
Involvement of phospholipase D in caerulein-induced phosphatidylcholine hydrolysis in rat pancreatic acini.
Rydzewska G, Rossignol B, Morisset J.
Departement de Biologie, Faculte des Sciences, Universite de Sherbrooke, Quebec, France.
Phosphatidylcholine (PC) metabolism stimulated by caerulein (Cae), a cholecystokinin analogue, was investigated in rat pancreatic acini prelabeled with [3H]choline or [3H]-myristic acid. Both labels were incorporated mostly into PC. An inhibition of choline incorporation into PC was first observed in response to Cae (100 and 500 pM) stimulation, as indicated by reduced [3H]choline incorporation into trichloroacetic acid-precipitable material. Whereas choline incorporation was reduced in PC, Cae (500 pM) significantly increased [3H]choline metabolites release in the incubation medium. Separation of these metabolites by thin-layer chromatography showed that approximately 90% of the labeled products released into the medium was phosphocholine; however, Cae caused significant increases of [3H]choline release after 5, 15, and 30 min. In response to Cae, manoalide, a phospholipase C (PLC) inhibitor, totally prevented phosphocholine release into the medium but did not affect choline release. Staurosporine, a protein kinase C inhibitor, did not influence basal and Cae-induced choline release. In cells prelabeled with [3H]myristic acid, Cae stimulated within 5 min a rapid increase in intracellular [3H]phosphatidic acid (PA) levels in the presence of the PA phosphohydrolase inhibitor, propranolol; this PA production was further increased after 15 and 30 min of stimulation. The time course of [3H]PA formation in the presence of propranolol was similar to that of choline release in the medium. Staurosporine partially blocked PA accumulation stimulated by Cae after 30 min. In contrast, manoalide significantly reduced basal PA accumulation but did not prevent its production in response to Cae. In the presence of ethanol, Cae also significantly stimulated above control values the formation of [3H]phosphatidylethanol. These data indicate that Cae-induced PC hydrolysis in rat pancreatic acini is mediated mostly by phospholipase D (PLD) to produce PA and choline; they suggest a direct action of Cae on PLD activation, an effect independent of PLC activation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8238356&dopt=Abstract
Arch Toxicol. 1993;67(7):478-90.
Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract.
Vijayaraghavan R, Schaper M, Thompson R, Stock MF, Alarie Y.
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA 15261.
A system was developed for exposure of unanesthetized mice to airborne chemicals and for continuous measurement of their breathing pattern prior to, during and following exposure. By measuring inspiratory and expiratory airflows (VI and VE), and integration with time to yield tidal volume (VT), we obtained characteristic modifications to the normal breathing pattern. These permitted recognition that a specific portion of the respiratory tract was affected by the selected airborne chemicals. Following recognition, we also quantitated the degree of effect using one specific measurement in each case. An effect on the upper respiratory tract, induced by the sensory irritant, 2-chlorobenzylchloride, was quantitated by measuring a decrease in respiratory frequency. An effect on the conducting airways, induced by the airway constrictor, carbamylcholine, was quantitated by a decrease in VE at the mid-point of VT. An effect at the alveolar level, induced either by the vagal nerve ending stimulant, propranolol, or by the pulmonary irritant, machining fluid G, was quantitated by an increase in the length of a pause induced at the end of expiration. The system is easy to construct and operate and can be used to rapidly evaluate the effects of airborne chemicals on the respiratory tract.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8239997&dopt=Abstract
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