Exploring Zeptosecond Quantum Equilibration Dynamics: From Deep-Inelastic to Fusion-Fission Outcomes in

Energy dissipative processes play a key role in how quantum many-body systems dynamically evolve toward equilibrium. In closed quantum systems, such processes are attributed to the transfer of energy from collective motion to single-particle degrees of freedom; however, the quantum many-body dynamics of this evolutionary process is poorly understood. To explore energy dissipative phenomena and equilibration dynamics in one such system, an experimental investigation of deep-inelastic and fusion-fission outcomes in the ^{58}Ni+^{60}Ni reaction has been carried out. Experimental outcomes have been compared to theoretical predictions using time dependent Hartree-Fock and time dependent random phase approximation approaches, which, respectively, incorporate one-body energy dissipation and fluctuations. Excellent quantitative agreement has been found between experiment and calculations, indicating that microscopic models incorporating one-body dissipation and fluctuations provide a potential tool for exploring dissipation in low-energy heavy ion collisions.

V-cryo-plate procedure as an effective protocol for cryobanks: case study of mint cryopreservation.

A vitrification procedure using aluminium cryo-plates (V-Cryo-plate procedure) was successfully developed and adjusted for in vitro-grown mint (Mentha spp.) shoot tips. Shoots were cultured at 25°C on MS medium containing 0.088 M sucrose for 7 to 14 days after the last subculture. Shoot tips with a basal part (1-1.5 mm × 1 mm) were dissected from the shoots and precultured at 25°C for 1 day on the same medium. Precultured shoot tips were placed on aluminium cryo-plates with 10 wells and embedded in alginate gel. Osmoprotection was performed by immersing the cryo-plates for 30 min at 25 degree C in 25 ml pipetting reservoirs filled with loading solution (2 M glycerol + 0.8 M sucrose). For dehydration, the cryo-plates were transferred and immersed in 25 ml pipetting reservoirs filled with PVS2 for 20 min at 25 degree C. Then the cryo-plates were transferred in uncapped 2 ml cryotubes and directly plunged into liquid nitrogen. For rewarming, shoot tips attached to the cryo-plates were immersed in cryotubes containing 2 ml 1 M sucrose solution at room temperature. Using this procedure, regrowth of cryopreserved shoot tips of line 'Fukuyamajisei' reached over 90 percent. This protocol was successfully applied to 16 additional Mentha lines, with regrowth ranging from 73 percent to 100 percent. This V-Cryo-plate method will facilitate the cryostorage of mint germplasm in our genebank.

Neutral endopeptidase inhibitors potentiate substance P- and capsaicin-induced cough in awake guinea pigs.

To study the roles of substance P and endogenous neutral endopeptidase in mediating cough, we measured cough responses in awake guinea pigs in response to exogenous substance P and capsaicin aerosols in the presence and absence of the neutral endopeptidase inhibitors leucine-thiorphan and phosphoramidon. Substance P stimulated cough in very low concentrations (10(-17)-10(-16) M). In a second study where the investigator did not know whether substance P or diluent alone was aerosolized, substance P (10(-16) M) caused cough. Leucine-thiorphan (10(-5) M) and phosphoramidon (10(-5) M) potentiated substance P-induced cough; NEP inhibitors also potentiated capsaicin-induced cough significantly. These findings suggest that substance P is a potent stimulator of cough responses, that capsaicin-induced cough is mediated by substance P or another similar neuropeptide, and that cough responses are modulated by endogenous neutral endopeptidase.

Mast cell tryptase causes airway smooth muscle hyperresponsiveness in dogs.

Supernatants obtained by degranulation of dog mastocytoma cells greatly increased the sensitivity and the magnitude of the contractile response of isolated dog bronchial smooth muscle to histamine. The enhanced contractile response was reversed completely by H1-receptor antagonists and was prevented by an inhibitor of tryptase (a major protease released with histamine from secretory granules of mast cells). The potentiation of histamine-induced contractions was reproduced by active tryptase in pure form. The contractions due to the combination of histamine and purified tryptase were abolished by the Ca2+ channel blockers nifedipine and verapamil. The bronchoconstricting effects of KCl and serotonin, which, like histamine, contract airway smooth muscle by a mechanism predominantly involving membrane potential-dependent Ca2+ transport, were also potentiated by tryptase. However, the contractile effects of acetylcholine, which contracts dog airway smooth muscle by a mechanism independent of Ca2+ channels, were unaffected by tryptase. These findings show a striking promotion of agonist-induced bronchial smooth muscle contraction by mast cell tryptase, via direct or indirect effects on Ca2+ channels, and the findings therefore suggest a novel potential mechanism of hyperresponsiveness in dog bronchi.

Association analysis of tissue inhibitor of metalloproteinase2 gene polymorphisms with COPD in Egyptians.

Proteinase/antiproteinase imbalance is recognized to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). A relative increase in the activities of matrix metalloproteinases might be caused by mutations of tissue inhibitor of metalloproteinase2 (TIMP2). Recently, two polymorphisms of the TIMP2 gene, +853 G/A and -418 G/C (+551 and -720 from the translation initiation site), have been shown to be associated with the development of COPD in the Japanese population. In this study, a case-control association analysis for these polymorphisms was conducted in the Egyptian population using 106 COPD patients and 72 healthy controls. The genotype frequency of +853 G/A was significantly different between the patient and the control groups (P = 0.029), although no significant difference was detected in the allele frequency between the two groups. These results suggest that the +853 G/A polymorphism of the TIMP2 gene might be associated with COPD across ethnicities. In contrast, neither the distributions of genotype nor allele frequencies of -418 G/C were significantly different between the two groups, raising the possibility that a combination of different genetic factors contributes to the development of COPD in different ethnic groups.

High incidence of pneumonia in elderly patients with basal ganglia infarction.

BACKGROUND: Pneumonia is a major cause of death in patients with cerebral infarction. We assessed morbidity associated with pneumonia in 276 patients 65 years of age or older who were admitted to a long-term care facility. Furthermore, we studied the swallowing reflex during the day and at night and monitored the occurrence of silent aspiration during sleep. OBJECTIVES: To examine the possible relationship between the location of cerebral hemispheric infarctions and the incidence of pneumonia and to evaluate the role of silent aspiration in the development of pneumonia. METHODS: The incidence of pneumonia was analyzed in 4 groups of patients who were assigned to a group on the basis of the following computed tomographic findings: no infarct (group A); 1 or more unilateral basal ganglia infarcts (group B); bilateral basal ganglia infarcts (group C); and 1 or more cerebral hemispheric infarcts outside the basal ganglia (group D). Criteria for diagnosis of pneumonia were (1) a new pulmonary infiltrate seen on a chest radiograph and (2) 1 or more of the following features: cough, temperature greater than 37.8 degrees C, or subjective dyspnea. Before the study, the patients with stroke were followed up for more than 1 year after their ictus and were monitored to determine if they sustained affecting cerebral hemispheric structures. The average duration of observation for incidence of pneumonia was 22 months. To study the swallowing reflex and to monitor for the occurrence of silent aspiration during sleep, 15 of the patients who were confined to bed or chair were randomly selected from each of groups A through C. The swallowing reflex was examined at both 1 PM and 1 AM and was evaluated according to latency of response, which was timed from the injection of 1 mL of distilled water into the pharynx through a nasal catheter to the onset of swallowing. The incidence of silent aspiration during sleep was examined using indium-111 chloride as a radioactive tracer attached to the teeth, and scanning of the thorax was performed the next morning. RESULTS: The incidence of pneumonia was 2.12 times higher in the patients of group B (27.4%; P < .01) and 3.64 times higher in the patients of group C (47.0%; P < .001) than in the patients of group A (12.9%). The latency of response was longer in the patients of groups B (P < .05) and C (P < .001) than in those of group A at 1 AM. The percentage of positive scans was also higher in the patients of groups B (P < .01) and C (P < .001) than in those of group A. CONCLUSION: Basal ganglia strokes might predispose these patients to develop pneumonia owing to frequent aspiration during sleep.

Atelectasis of the right medial basal segment mimicking primary lung cancer in an asthmatic patient.

A segmental collapse due to mucous plug in the bronchus tree may mimic malignant pathological conditions. We present a case of 58-year-old asthmatic patient with an obstruction of right medial basal bronchus due to mucous plug, which was simulating mediastinal mass. To the best knowledge, a similar case is not reported in the English medical literature.

The role of nitric oxide in cholinergic neurotransmission in rat trachea.

1. We have investigated the role of nitric oxide (NO) in cholinergic contraction in rat trachea. 2. Methylene blue (10 nM to 30 microM) potentiated cholinergic contraction induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent fashion. At a concentration of 30 microM, methylene blue decreased responses to log EFS frequency, producing 50% of maximum contraction from a control value of 0.74 +/- 0.09 Hz to 0.30 +/- 0.05 Hz without a significant effect on concentration-response curves to acetylcholine (ACh). 3. NG-monomethyl-L-arginine (L-NMMA; 100 microM) also potentiated cholinergic contraction induced by EFS at 5 Hz (131.5 +/- 4.6% of control) without having any effect against ACh (3 microM)-induced contractions. Likewise, L-NMMA (100 microM) significantly increased EFS (5 Hz)-evoked release of ACh from tracheal segments into the bath solution (51.4 +/- 4.0 pmol ml-1 in the presence of L-NMMA and 35.0 +/- 1.8 pmol ml-1 in the absence of L-NMMA, respectively). 4. Administration of NO (present in acidified solution of NaNO2) (1 nM to 10 microM) and sodium nitroprusside (100 nM to 10 microM) concentration-dependently reduced EFS (5 Hz)-induced cholinergic contractions without having a significant effect on ACh (3 microM)-induced contractions. These results were unaffected by prior exposure of the tissues to L-NMMA (100 microM). 5. Dibutyryl cyclic GMP (3 mM) also reduced cholinergic contractions induced by EFS at 5 Hz (70.1 +/- 3.6% of control) without any significant effect on ACh (3 microM)-induced contractions. 6. Pretreatment of tissues with capsaicin (30 microM) or a-chymotrypsin (1 u ml-') failed to inhibit methylene blue (30 microM)-induced potentiation of responses to EFS at 5 Hz.7. These results suggest that an endogenous NO-like factor may mediate prejunctional inhibition of cholinergic contraction through a cyclic GMP-dependent mechanism in rat trachea.

Inhibitory actions of prostaglandin E1 on non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

We have investigated the effect of prostaglandin E1 (PGE1) on non-adrenergic, non-cholinergic (NANC) contraction in guinea-pig bronchial strips. PGE1 (10 nM to 10 microM) did not alter baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 6.60 +/- 0.10 M and maximum inhibition was 88.7 +/- 2.9%). PGE1 (greater than 0.3 microM) also reduced the contraction induced by substance P (1 microM). Removal of epithelium did not alter the effects of PGE1 on NANC contraction. These results suggest that PGE1 exerts both pre- and post-junctional inhibitory actions on NANC contraction.

The role of cyclic AMP in non-adrenergic non-cholinergic contraction in guinea-pig bronchi.

1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 was 7.22 +/- 0.12 M and maximum inhibition was 100 +/- 0.01%). However, forskolin (less than 1 microM) did not alter the contraction induced by substance P (SP, 1 microM). 3. Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions induced by EFS (100 +/- 0.01%) without significant effect on SP (1 microM)-induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect against either NANC or SP-induced contractions. 4. Both the beta 2-adrenoceptor agonist, procaterol (0.1 nM to 3 nM) and theophylline (100 nM to 1 mM) concentration-dependently reduced EFS-induced NANC contractions without significant effect on SP (1 microM)-induced contractions. 5. In contrast to forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim inhibited the EFS-induced contractions only at those concentrations that similarly reduced the contractions induced by SP (1 microM). 6. These results suggest that cyclic AMP may mediate pre-junctional inhibition of NANC contractions in guinea-pig bronchi.

Effects of adrenomedullin and calcitonin gene-related peptide on airway and pulmonary vascular smooth muscle in guinea-pigs.

1. The airway and pulmonary vascular effects of adrenomedullin were studied in the guinea-pig isolated trachea, main bronchi and pulmonary artery in vitro and compared to the effects of calcitonin gene-related peptide (CGRP). 2. In tracheal rings, CGRP (1 nM to 1 microM) potentiated the cholinergic contractions induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent manner. At a concentration of 1 microM, CGRP slightly decreased the responses to log EFS frequency, producing 50% of the maximum contraction from a control value of 0.77 +/- 0.10 Hz to 0.54 +/- 0.05 Hz without a significant effect on the concentration-response curves to acetylcholine (ACh). In contrast, adrenomedullin (1 nM to 1 microM) did not alter either EFS-induced cholinergic or ACh-induced contractions. 3. In bronchial strips, CGRP (1 nM to 1 microM) slightly reduced both the non-adrenergic non-cholinergic (NANC) contraction induced by EFS at 10 Hz and the substance P (1 microM)-induced contraction in a concentration-dependent manner, whereas adrenomedullin (1 nM to 1 microM) was without effect. 4. Neither CGRP (1 microM) nor adrenomedullin (1 microM) altered NANC relaxation induced by EFS at 5 Hz in tracheal rings precontracted with histamine (10 microM). 5. Adrenomedullin (1 nM to 1 microM) and CGRP (1 nM to 1 microM) induced a concentration-dependent relaxation of the histamine (10 microM)- and prostaglandin F2 alpha (10 microM)-precontracted pulmonary arterial rings with intact endothelium with a similar potency. 6. Neither removal of the endothelium nor NG-nitro-L-arginine methyl ester (100 microM) altered the vasorelaxant effects of adrenomedullin (1 nM to 1 microM) and CGRP (1 nM to 1 microM). 7. The putative CGRP receptor antagonist, CGRP8-37 (1 microM to 10 microM) concentration-dependently attenuated the CGRP (3 nM to 30 nM)-induced vasorelaxant actions, whereas it had no effect on the relaxation of vessel rings induced by adrenomedullin (3 nM to 30 nM). 8. These results suggest that adrenomedullin is a potent vasodilator of the pulmonary artery without any bronchomotor effect in the guinea-pig lung, and that the vasorelaxant actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.

Expression of hnRNP A2/B1 proteins in human cancer cell lines.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is recently reported informative as a marker of lung cancer for early detection. To examine whether the expression of the proteins is specific for lung cancer, immunological analyses were performed both in lung and non-lung cancer cell lines. In immunostaining and Western blotting, the expression of A2/B1 was observed not only in the lung cancer cells but also in non-lung cancer cells. The expression of hnRNP A2/B1 is not specific for lung cancer and quantitative determination of A2/B1 is required to elucidate their significance in carcinogenesis.

Erythromycin and common cold in COPD.

STUDY OBJECTIVES: To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN: Prospective, randomized, controlled, but not blinded, trial. PATIENTS: One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or to no active treatment in September 1997. Patients then were observed for 12 months, starting in October, during which time the risk and frequency of catching common colds and COPD exacerbations were investigated. Fifty-five patients received erythromycin at study entry (erythromycin group). The remaining 54 patients received no active treatment (control group). MEASUREMENTS AND RESULTS: The mean (+/- SE) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group (1.24 +/- 0.07 vs 4.54 +/- 0.02, respectively, per person; p = 0.0002). Forty-one patients (76%) in the control group experienced common colds more than once, compared to 7 patients (13%) in the erythromycin group. The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 (95% confidence interval [CI], 3.92 to 31.74; p = 0.0001). Thirty patients (56%) in the control group and 6 patients (11%) in the erythromycin group had one or more exacerbations. The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 (95% CI, 1.53 to 14.5; p = 0.007). Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group (p = 0.0007). CONCLUSION: Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients.

Mechanisms of gastric juice-induced hyperpermeability of the cultured human tracheal epithelium.

PURPOSE: The respiratory aspiration of the stomach contents causes severe lung damage called aspiration pneumonia. The present study was undertaken to elucidate whether mucosal exposure of gastric juice causes hyperpermeability of the human airway epithelium and to determine the mechanisms responsible for gastric juice-induced airway epithelial damage. MATERIALS AND METHODS: Gastric juice was collected from 46 normal adults via gastroscope and samples were analyzed for pH, osmolarity, and concentration of pepsin and trypsin. Tracheal surface epithelial cells were obtained from 16 autopsies, cultured onto porous filters, and mounted in the Ussing chamber. Electrical conductance (G) was measured before and after exposure of cells to gastric juice or Krebs-Henseleit solution with pH at 1.8, 2.8, 4.0, or 7.4 in the presence or absence of pepsin. D-[3H] mannitol flux study across the epithelial layer and histologic observations using an inverted microscope were also performed after exposure of cells to gastric juice. RESULTS: Exposure of cultured human tracheal epithelium to gastric juice caused increases in G in a time- and pH-dependent fashion. A pepsin inhibitor (pepstatin A) inhibited gastric juice-induced increases in G at a pH of 2.8, and the addition of pepsin augmented increases in G induced by the Krebs-Henseleit solution at a pH of 1.8 and 2.8. Lowering the osmolarity of the solution to levels similar to gastric juice also potentiated increases in G induced by acid and pepsin. Gastric juice caused increases in D-[3H] mannitol flux across the epithelial layer bidirectionally, and microscopic observation revealed separation of the intercellular space and cell detachment from culture vessels after exposure of cells to gastric juice. CONCLUSION: Gastric juice causes hyperpermeability across human airway epithelium probably through the additive effects of gastric acid, pepsin activity, and lower osmolarity.

Laryngeal resistance immediately after panting in control and constricted airways.

Laryngeal resistance (Rla) in the postpanting interval (PPRla) was examined in five normal subjects in the control state and with methacholine- and histamine-induced bronchoconstriction. Respiratory resistance (Rrs) was measured by the forced oscillation technique at 10 Hz, and Rla was measured by the low-frequency sound method (Sekizawa, K., C. Shindoh, W. Hida, S. Suzuki, et al. J. Appl. Physiol. 55:591-597, 1983). Inspiratory Rrs (IRrs) was lower than expiratory Rrs (ERrs), and Rrs immediately after panting (PPRrs) was not significantly different from IRrs in the three airway conditions. Rla increased with bronchoconstriction and inspiratory Rla (IRla) was lower than expiratory Rla (ERla). PPRla was lower than IRla (P less than 0.01) by an amount corresponding to the decrease in Rrs in the control airway. However, in constricted airways, PPRla was higher than IRla and about the same as ERla. We suggest that the panting maneuver is suitable for minimizing the effect of laryngeal artifact in the control airway, but in the constricted airway the panting maneuver may fail to cause widening of the laryngeal orifice.

Control of larynx during loaded breathing in normal subjects.

We examined laryngeal resistance (Rla) in six normal subjects in control and four kinds of loaded breathing: hypercapnia, chest strapping, added external resistance, and inhaled methacholine. Rla was measured with a low-frequency sound methed (Sekizawa et al., J. Appl. Physiol. 55: 591-597, 1983). In control and the four kinds of loaded breathing, changes in Rla were tightly coupled with ventilation and Rla decreased during inspiration and increased during expiration. Hypercapnia and chest strapping significantly decreased Rla in both inspiration and expiration in all subjects. Added external resistance decreased inspiratory Rla in all subjects, but decreased expiratory Rla in three subjects, did not change it in two subjects, and increased it in one subject. Inhaled methacholine increased Rla in both inspiration and expiration in all subjects. The present study suggests that although laryngeal movement is tightly coupled with ventilation, laryngeal aperture may be determined by the complex competition of dilating and constricting mechanisms associated with the activity of the respiratory center and neural reflexes from the airway.

Effect of a previous voluntary deep breath on laryngeal resistance in normal and asthmatic subjects.

We studied changes in both laryngeal resistance (Rla) and respiratory resistance (Rrs) after a voluntary deep breath in 7 normal and 20 asthmatic subjects. Rla was measured using a low-frequency sound method (Sekizawa et al. J. Appl. Physiol. 55: 591-597, 1983) and Rrs by forced oscillation at 3 Hz. In normal subjects, both Rla and Rrs significantly decreased after a voluntary deep breath (0.05 less than P less than 0.01). During methacholine provocation in the normal subjects, a voluntary deep breath significantly decreased Rrs (0.05 less than P less than 0.01, but Rla was significantly increased (0.05 less than P less than 0.01). In 10 asthmatic subjects in remission, a voluntary deep breath significantly increased Rrs (0.05 less than P less than 0.01) but significantly decreased Rla (0.05 less than P less than 0.01). In another 10 asthmatic subjects during spontaneous mild attacks, a voluntary deep breath significantly increased both Rrs and Rla (0.05 less than P less than 0.01). The present study showed that without obvious bronchoconstriction, Rla decreased after a voluntary deep breath in both normal and asthmatic subjects but, with bronchoconstriction, Rla increased in both groups. Subtraction of the change in Rla from Rrs gives the change in Rrs below the larynx (Rlow). Rlow changed little or decreased in normal subjects and increased in asthmatic subjects, irrespective of base-line bronchomotor tone. These results suggest that airway response below the larynx after a voluntary deep breath differentiates patients with bronchial asthma from normal subjects.

Somatostatin potentiates cholinergic neurotransmission in ferret trachea.

We studied the effect of somatostatin on contractile responses to electrical field stimulation (EFS) in isolated ferret tracheal segments. Somatostatin (up to 10(-5) M) did not change resting tension, but it potentiated the contractile response to EFS dose dependently, with a maximum effect at 10(-6) M. Thus, at a concentration of 10(-6) M, somatostatin significantly decreased the mean log of EFS frequency producing 50% of maximum contraction from a control value of 0.52 +/- 0.07 to 0.24 +/- 0.06 (SE) Hz (P less than 0.01). The potentiating effect of somatostatin (10(-6) M) was not inhibited by hexamethonium, indomethacin, BW755C, pyrilamine, methysergide, or D,Pro2,D,Trp7,9-SP, but it was inhibited by atropine or by the somatostatin antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)]. In contrast to EFS-induced contraction, contractions produced by acetylcholine (10(-9) to 10(-3) M) were not affected by somatostatin at a concentration of 10(-6) M. These results suggest that somatostatin potentiates contractions produced by EFS via presynaptic cholinergic mechanisms and probably through a specific somatostatin receptor.

Modulation of cholinergic neurotransmission by vasoactive intestinal peptide in ferret trachea.

We studied the effect of vasoactive intestinal peptide (VIP) on the contractile responses to electrical field stimulation (EFS) in isolated ferret tracheal segments. VIP did not change resting tension up to 2 X 10(-7) M, but it showed a biphasic effect on the responses to EFS. In concentrations up to 10(-9) M, VIP potentiated the response; at higher concentrations VIP reduced responses. Thus, at a concentration of 10(-9) M, VIP decreased the mean (+/- SE) log EFS frequency, producing 50% of maximum contraction significantly from a control value of 0.476 +/- 0.062 to 0.214 +/- 0.057 Hz (P less than 0.01); at a concentration of 2 X 10(-7) M VIP increased the half-maximal frequency from a control value of 0.513 +/- 0.086 to 0.752 +/- 0.053 Hz (P less than 0.05). The potentiating effect of VIP (10(-9) M) was not inhibited by hexamethonium, indomethacin, pyrilamine, methysergide, or [D-Pro2,D-Trp7,9] substance P. The inhibitory effect of VIP (2 X 10(-7) M) was also not inhibited by hexamethonium, indomethacin, or naloxone. In contrast to EFS-induced contraction, contractions produced by acetylcholine (10(-9) to 10(-3) M) were not affected by VIP at concentrations of 10(-9) and 2 X 10(-7) M. These results suggest that VIP modulates contractions produced by EFS via presynaptic cholinergic mechanisms and probably through a specific VIP receptor.

Nonadrenergic inhibitory nerves attenuate neurally mediated contraction in cat bronchi.

Effects of nonadrenergic and noncholinergic (NANC) inhibitory nerves on cholinergic neurotransmission were examined in isolated bronchial segments from cats in the presence of propranolol (10(-6) M) and indomethacin (10(-6) M) by use of electrical field stimulation (EFS) techniques. EFS caused contraction alone in tissues at the baseline tension and biphasic responses (contraction and relaxation) in tissues precontracted with 5-hydroxytryptamine. Contraction was abolished by atropine (10(-6) M), and relaxation was abolished by tetrodotoxin (10(-6) M). At the baseline tension, EFS at frequencies greater than 10 Hz inhibited the subsequent (4 min later) contraction induced by EFS at 1-5 Hz. EFS-induced inhibition was stimulus frequency dependent and reached maximum at 20 Hz. However, EFS at 20 Hz did not inhibit the subsequent contractile response to acetylcholine (10(-7) to 10(-3) M). Exogenously applied vasoactive intestinal peptide mimicked EFS-induced inhibitory effects, but substance P and calcitonin gene-related peptide did not. The inhibitory effect of EFS at 20 Hz was not altered by pyrilamine, cimetidine, naloxone, methysergide, phentolamine, BW755C, AF-DX 116, or removal of epithelium. These results imply that the NANC transmitter acts via presynaptic cholinergic receptors.