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At least 127 records · Page 7Linked to original sources
PubMed1986

Cholinergic receptors in the upper respiratory system of the rat.

Radioligand receptor binding might give more detailed information on the innervation pattern of the nasal mucosa and the character of the various neuroreceptors involved. With respect to the cholinergic receptors, this technique reveals that specific binding of tritiated I-quinuclidinyl benzilate to rat nasal mucosa homogenates occurs to a homogeneous class of binding sites, with a dissociation constant of 0.06 +/- 0.02 nM and a receptor density of 8 +/- 2 pmole/g of tissue. Binding is stereoselectively inhibited by benzetimide hydrochloride enantiomers. Pirenzepine displacement (inhibition constant = 0.5 X 10(-6) M) classifies tritiated I-quinuclidinyl benzilate binding sites as M2-muscarinic receptors. Methylfurthrethonium inhibits tritiated I-quinuclidinyl benzilate binding at high concentrations, pointing to the presence of low-affinity agonist binding sites, probably admixed with a small proportion of high-affinity agonist binding sites. These data obtained in the rat open new perspectives for studying muscarinic receptors in the human nose to elucidate the supposed disturbance of autonomic nerve regulation in nasal hyperreactivity.

Animals↗
PubMed1986

Acute effects of routine firefighting on lung function.

We undertook a study to determine the acute effects of routine firefighting on lung function and the relationship between these acute effects and nonspecific airway responsiveness. For 29 firefighters from a single fire station, we calculated the concentration of methacholine aerosol that caused a 100% increase in specific airway resistance (Pc100). Over an 8-week period we than measured FEV1 and FVC in each firefighter before and after each 24-hr workshift and after every fire. From 199 individual workshifts without fires, we calculated the mean +/- 2 SD across-workshift change in FEV1 and FVC for each firefighter. Eighteen of 76 measurements obtained within 2 hr after a fire (24%) showed a greater than 2 SD fall in FEV1 and/or FVC compared to two of 199 obtained after routine workshifts without fires (1%; p less than .001). On 13 of 18 occasions when spirometry decreased significantly, we obtained repeat spirometry (postshift) 3-18.5 hr after fires, and on four of these occasions FEV1 and/or FVC were still more than 2 SD below baseline. Decrements in spirometry occurred as often in firefighters with high Pc100s as in those with low Pc100s. In two firefighters in whom FEV1 and FVC fell by more than 10% after fires, we repeated measurements of methacholine sensitivity, and it was increased over the prestudy baseline. These findings suggest that routine firefighting is associated with a high incidence of acute decrements in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Respiratory disease in a photographer.

Reversible airways obstruction occurred in a photographer after long-term exposure (over many years) to sulfuric and acetic acid fixers. Air-exchange recommendations for darkrooms by the Building Officials Code Administration [1981] differ markedly from those recommended by the American Society of Heating, Refrigerating, and Airconditioning Engineers [1977] and the fixer manufacturer (Eastman Kodak). Use of fume hoods or rates of air-exchange higher than are required by law may be necessary to prevent symptoms and disease in certain workers.

Adult↗
PubMed1990

Extracellular sodium is required for methacholine-induced secretion of mucus glycoconjugates from canine tracheal explants.

Extracellular sodium is known to influence secretion by certain secretory cells, possibly by mobilizing calcium from cellular stores or by altering intracellular pH via regulation of a Na(+)-H+ antiport system. Using canine tracheal explants, we determined whether agents which alter sodium fluxes are capable of modulating basal or cholinergically-induced secretion of mucus glycoconjugates. Methacholine, a cholinergic agonist, increased mucus secretion from explants incubated in the presence or absence of calcium, but had no effect on secretion when incubated in sodium-deficient media, indicating (a) that cholinergically-induced secretion can be mediated by mobilization of cellular calcium and (b) that extracellular sodium was required for this stimulatory effect. Several agents which increase intracellular sodium were tested for their effect on mucus secretion. Ouabain, a sodium pump inhibitor, and veratridine, a sodium channel activator, did not significantly affect control or methacholine-induced secretion; gramicidin, a sodium ionophore, also had no effect on basal release. Tetrodotoxin, a sodium channel inhibitor, was also without effect on basal or methacholine-stimulated mucus release. Agents which alter intracellular pH were also examined for their effects on basal or methacholine-induced glycoconjugate secretion. Amiloride, which decreases intracellular pH by inhibiting Na(+)-H+ exchange, produced a 19 per cent increase in basal secretion (not statistically significant), but had no effect on methacholine-induced secretion. An agent, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which decreases intracellular pH by inhibiting HCO3(-)-Cl- exchange, elicited decreases in both basal and methacholine-induced secretion, but the inhibition did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1982

Methacholine provocation of Prinzmetal's variant angina pectoris: a revised perspective.

We report 13 patient with unequivocal Prinzmetal's variant angina pectoris as the entire experience with this syndrome during a 7-year period in a single institution. The clinical diagnosis of this relatively uncommon disorder is emphasized. Five patients were given 10 mg of methacholine subcutaneously. Three demonstrated subsequent delayed appearance of chest pain, ECG change, and coronary vasospasm following early appearance of muscarinic effects. Two Prinzmetal patients had no provocation of variant angina following methacholine, though they did experience significantly less blood pressure fall in response to muscarinic provocation. Another 23 subjects with incompletely explained chest pain given methacholine had neither ECG change nor spasm. Methacholine provocation of variant angina need not necessarily implicated a parasympathomimetic mechanism for otherwise spontaneous episodes. Rather, provocation would appear to occur via the customary reflex adrenergic response to drug-induced hypotension. Methacholine is probably safe though unreliable as an agent to be used for spasm provocation.

Adult↗
PubMed1988

Duration of effect of gallopamil, a calcium channel blocker, on methacholine-induced bronchoconstriction.

We previously demonstrated a modest but significant protective effect of inhaled gallopamil (D600), the methoxy derivative of verapamil, against methacholine-induced bronchoconstriction; however, the duration of the protective effect of this and other calcium channel blockers is unknown. We therefore evaluated the duration of this protective effect in 15 asthmatic subjects in a prospective, placebo-controlled trial. Methacholine challenges (Cockcroft method) were performed 2 hours before and 30 minutes after the administration of placebo, and 1 mg and 10 mg of inhaled gallopamil. Gallopamil did not alter resting airway caliber, but significantly increased the concentration of methacholine required to decrease the FEV1 20% 30 minutes after the dose. Results with both the 10-mg and 1-mg doses were significantly different from placebo, but not from each other. The duration of this protective effect was transient in the group as a whole; the mean drug activity ratios were not significantly different with this sample 2.5 hours after the dose. Thus the short duration of effect limits the potential clinical usefulness of gallopamil in suppressing the signs and symptoms of chronic asthma.

Adolescent↗
PubMed1987

Differentiation-associated decrease in muscarinic receptor sensitivity in human neuroblastoma cells.

Muscarinic receptor-linked increases in intracellular free Ca2+ as measured with quin-2 and Ca2+ release from monolayers of cells have been measured in the human neuroblastoma cell line SH-SY5Y. Induction of differentiation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) leads to a decrease in the sensitivity of the cells to low concentrations of agonists with respect to the induced increase in cytosolic free Ca2+ and stimulation of Ca2+ efflux. No decrease in agonist binding affinity was observed when the displacement of a labelled antagonist, 3H-NMS, by a non-labelled agonist was studied.

Calcium↗
PubMed1989

Effect of inhaled ipratropium bromide on methacholine and exercise provocation in asthmatic children.

To determine whether doses of ipratropium bromide (IB) greater than those usually administered by aerosol (75-250 micrograms) give a greater degree of protection from exercise-induced asthma (EIA) in children, 12 patients with chronic asthma, ages 7-13 yr, were challenged with methacholine and exercise after inhalation of saline or 125, 250, 500, and 750 micrograms of IB on different days. A small and similar bronchodilation (mean increase over baseline: 5.26%) was observed 60 min after the administration of each dose of IB. IB prevented the bronchoconstriction caused by methacholine in all doses we used without statistically significant differences between them. All doses gave an all-or-none protection from EIA. Mean percent fall in FEV1 after exercise was 36.8, 18.3, 23.7, 27.1, and 23.2 following inhalation of saline or 125, 250, 500, or 750 micrograms of IB, respectively. The degree of protection from EIA was not correlated with the bronchodilation caused by IB. We suggest that muscarinic mechanisms are only partly responsible for the pathogenesis of EIA in children. Their importance varies among subjects and also may be variable in the same subject. Alternative mechanisms may be responsible for bronchoconstriction.

Administration, Inhalation↗
PubMed1989

Cholinergic modulation of frequency receptive fields in auditory cortex: I. Frequency-specific effects of muscarinic agonists.

Previously we reported that acetylcholine (ACh) and acetyl-beta-methacholine (MCh) modify responses of neurons in auditory cortex to individual frequencies. The purpose of this study was to determine whether muscarinic agonists produce frequency-specific alterations or general changes in cellular responses. Frequency-specific modifications would be evident in alterations of frequency receptive fields (FRF) that differed across frequencies while general effects would be seen as changes that were more or less the same over frequencies. Responses of single neurons to designated sets of tones were recorded in the auditory cortex of chronically prepared awake cats before, during, and following ejection of ACh or MCh by iontophoresis or micropressure using multibarrel micropipettes. Frequency receptive fields were determined by presenting isointensity tones across a range of frequencies including the cell's best frequency (BF) to tone onset. FRF for "off" and "sustained (through)" responses were also determined quantitatively. The effects of ACh and MCh were predominantly frequency-specific (77%, 39/51 cells); general changes (19%, 10/51) and no effects (4%, 2/51) were less likely. Frequency-specific effects involved both facilitation and reduction of the same response component to different frequencies within the same neuron. For responses to tone onset (but not "through" and "off" responses), agonists were more likely to produce a decrease at the BF while simultaneously increasing responses to other frequencies. Agonists could increase or decrease frequency selectivity. Effects of agonists could be blocked by atropine, suggesting involvement of muscarinic receptors.

Acetylcholine↗
PubMed1988

Methoctramine selectively blocks cardiac muscarinic M2 receptors in vivo.

The antimuscarinic effects of methoctramine (N, N'-bis[6-[(2-methoxybenzyl)amino]hexyl]-1, 8-octanediamine tetrahydrochloride), a polymethylene tetraamine endowed with high cardioselectivity in vitro, were assessed in two in vivo preparations. Methoctramine (300 micrograms/kg i.v.) strongly inhibited the methacholine- and muscarine-induced bradycardia in the anaesthetized an pithed rat, respectively. The same dose of methoctramine did not significantly affect the depressor action of methacholine in the anaesthetized rat mediated by vascular M2 receptors. Furthermore, even high doses of methoctramine (up to 1 mg/kg i.v.) did not reduce the ganglionic M1 receptor-mediated tachycardia and pressor response to muscarine or McN-A-343 in the pithed rat. These data suggest that methoctramine while showing high affinity for cardiac M2 alpha receptors has rather low affinity for ganglionic M1 and vascular M2 receptors. This in vivo study thus provides further evidence to support the view that methoctramine is a potent and highly selective antagonist of cardiac M2 alpha receptors.

Animals↗
PubMed1988

Effect of muscarinic receptor stimulation on release of cysteinyl-leukotrienes and thromboxane B2 from anaphylactic guinea-pig hearts.

The effects of muscarinic receptor stimulation by infusions of methacholine (6.25 x 10(-8) mol/min or 1.9 x 10(-7) mol/min) into isolated perfused, spontaneously beating sensitized guinea-pig hearts on the anaphylactic release of cysteinyl-leukotrienes (LT) and thromboxane (TX) B2 were investigated. Methacholine increased coronary flow and decreased heart rate under basal conditions. Furthermore, infusions of methacholine (1.9 x 10(-7) mol/min) significantly increased the anaphylactic release of TXB2 as well as of immunoreactive cysteinyl-LT, which were demonstrated by reversed phase high pressure liquid chromatography to consist of a mixture of LTC4, LTD4 and LTE4. Infusions of atropine (1.3 x 10(-7) mol/min) alone did not significantly affect coronary flow and heart rate prior to ovalbumin injection nor anaphylactic release of cysteinyl-LT. The anaphylactic release of TXB2 was, however, significantly decreased in the presence of atropine. Atropine (1.3 x 10(-7) mol/min) infused in addition to methacholine (1.9 x 10(-7) mol/min) abolished the effects of the muscarinic receptor agonist on spontaneous heart rate and significantly antagonized the increase in coronary flow prior to ovalbumin injection. Similarly, the simultaneous infusion of atropine abolished the effects of methacholine on the anaphylactic release of TXB2 and cysteinyl-LT. After antigen challenge hearts infused with methacholine, atropine or the combination of both drugs did not exhibit any differences with respect to anaphylactic changes of heart rate or the time course of anaphylactic coronary flow reduction. Thus, in the isolated perfused anaphylactic guinea-pig heart, muscarinic receptor stimulation significantly enhanced the release of the arachidonic acid-derived mediators TXB2 and cysteinyl-LT.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗
PubMedDate not supplied

Muscarine receptor types mediating autoinhibition of acetylcholine release and sphincter contraction in the guinea-pig iris.

The potencies of several muscarine receptor antagonists in blocking either the autoinhibition of acetylcholine release or the muscarinic contraction of the sphincter muscle upon acetylcholine release were investigated in the guinea-pig iris. The agonist at pre- or postjunctional muscarine receptors was acetylcholine released upon field stimulation (5.5 Hz, 2 min) of the irides preloaded with 14C-choline. The stimulation-evoked 14C-overflow was doubled in the presence of atropine 0.1 mumol/l but unaffected by the agonist (+/-)-methacholine (50 mumol/l). Thus, under the present stimulation conditions, the autoinhibition of acetylcholine release on the guinea-pig iris cholinergic nerves was nearly maximally activated. Isotonic contractions of the irides upon field stimulation consisted of a rapid, atropine (0.1 mumol/l)-sensitive peak phase followed by a sustained contraction which involved a cholinergic and a non-cholinergic stimulation of the sphincter muscle. The M2-selective antagonists methoctramine (10 mumol/l) and gallamine (100 mumol/l) increased both the 14C-overflow and the peak contractions evoked by field stimulation. In contrast, the M3-selective antagonist hexahydrosiladifenidol (0.1-10 mumol/l) failed to affect the evoked 14C-release but concentration-dependently (1-10 mumol/l) reduced the iris contractions. Pirenzepine (10 mumol/l) enhanced the evoked 14C-overflow and inhibited the peak contractions (0.1-10 mumol/l; maximal effect at 10 mumol/l). The low potency of the antagonist at both receptor sites indicates that an M1 muscarine receptor is not involved. The results are consistent with the idea of M2 muscarine receptors mediating autoinhibition of acetylcholine release in the guinea-pig iris and M3-like receptors inducing the contraction of the sphincter muscle.

Acetylcholine↗
PubMed1987

Epidemiological diagnosis of asthma: methodological considerations of prevalence evaluation.

Within an epidemiological survey on Chronic Obstructive Pulmonary Disease, before reporting data on the prevalence of bronchial asthma we checked the group of subjects defined as "pathological" by means of a suitable questionnaire and a group of "normals" as a control. We evaluated the sensitivity and specificity of the questionnaire, in comparison with a clinical evaluation made by two physicians and controlled the relationship among their results, non-specific bronchial hyperreactivity and skin tests. In particular the correspondence between diagnosis made by physicians from a clinical evaluation and that obtained by questionnaire was not satisfactory. We suggest the importance of employing physicians for an epidemiological approach to asthma, in absence of a valid objective criterion.

Adolescent↗
PubMed1984

Scanning electron microscopy of nasal arterioles effected by vasoactive agents.

Morphological changes in nasal blood vessels induced by alpha- and beta-adrenergic and cholinergic agonists were studied under a scanning electron microscope after removal of extracellular connective tissue and the basal lamina. Arterioles were constricted and dilatated following topical application of alpha-adrenergic and cholinergic agonists. Distinctive morphological changes were observed on their smooth muscle cells. Smooth muscle cells of constricted arterioles had a rugged surface with numerous fine invaginations. However, in dilatated arterioles the cells had a smooth surface and intercellular spaces were clearly revealed. No remarkable changes were produced in smooth muscle cells by the beta-adrenergic agonist. It is concluded that nasal arterioles are sensitive to alpha-adrenergic and cholinergic stimulation but not to beta-adrenergic stimulation.

Animals↗
PubMed1985

Substance P antagonists and mucociliary activity in rabbit.

Substance P (SP) is known to accelerate mucociliary (m.c.) activity in the rabbit maxillary sinus in vivo. The physiological significance of this finding was investigated by testing three putative SP antagonists. [Arg5, D-Trp7,9, Nle11]SP5-11 could not be used as an antagonist because it stimulated m.c. activity. [D-Arg1, D-Trp7,9, Leu11]SP had no effect on the m.c. activity changes induced by SP. [D-Pro2, D-Trp7,9]SP was found to be an effective antagonist, 1 mg/kg of this drug reversibly inhibiting both the effects of 0.1 micrograms/kg SP and the stimulating effect of 1.0 micrograms/kg bradykinin and 30.0 micrograms/kg capsaicin; the stimulating effect of 0.5 micrograms/kg methacholine was not inhibited. It is suggested that bradykinin and capsaicin stimulate m.c. activity at least partly by releasing SP. The results of this investigation also support the view that the accelerating effect of SP on m.c. activity reflects physiological SP-mediated protective mechanisms in the airways. It is concluded that [D-Pro2,D-Trp7,9]SP is a useful pharmacological tool for studying the role of SP in the control of m.c. activity in rabbits.

Animals↗