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M Yu

Publications and source records attributed to M Yu.

At least 361 records · Page 20Linked to original sources

Isolation of a peptide that inhibits the posttranslational arginylation of proteins in rat brain.

All eukaryotic cells contain enzymes that are able to catalyze the transfer of Arg from tRNA to the N-terminus of naturally short lived or damaged cytosolic proteins. For certain test proteins, it has been shown that the addition of Arg to the N-terminus leads to their degradation via the ubiquitin proteolytic pathway. The mechanisms used by cells for identifying proteins for arginylation and regulating arginylation are not known. The present study reports the isolation of a peptide from rat brain that is able to inhibit the arginylation of proteins in brain extracts. We suggest that this peptide is the physiological regulator of arginylation in rat brain.

Animals↗

Independent modulation of horse airway smooth muscle by epithelium and prostanoids.

The effects of epithelial removal and cyclooxygenase inhibition on contractions induced by exogenous acetylcholine (ACh) and electrical field stimulation (EFS) were evaluated in horse tracheal strips and bronchial rings. Epithelial removal potentiated the response to ACh but had no influence on the response to EFS. The effect of epithelial removal was not altered by pretreating the tissues with meclofenamate, a cyclooxygenase inhibitor. In trachealis strips, meclofenamate augmented contractions induced by EFS but not by ACh. In bronchial rings, meclofenamate augmented EFS-induced contraction to a greater extent than ACh-induced contraction. These effects of meclofenamate were epithelium-independent. We conclude that horse airway epithelium produces a relaxant factor that is not a prostanoid. Endogenous prostanoids originating from non-epithelial sites inhibit only cholinergic nerves in the trachea but both parasympathetic nerves and smooth muscle in the bronchi.

Acetylcholine↗

Cloning and nucleotide sequence determination of the major envelope glycoprotein (gp55) gene of hog cholera virus (Weybridge).

A 1.7 kb cDNA fragment corresponding to the coding region of the major envelope glycoprotein (gp55) of pestivirus hog cholera (Weybridge) was obtained using the polymerase chain reaction (PCR), and then cloned into pUC 8. The deduced amino acid sequence of gp55 showed a strong homology to that of HCV strains Brescia (94%) and Alfort (90%), and to a lesser extent to the closely related gp53 of bovine viral diarrhoea virus strain, NADL (65%). Eighteen cysteine residues were identified in the sequenced region, all of which were conserved between the gp55/gp53 sequences. This suggests that although the homology at the protein level may vary, there are strong conformational motifs which are conserved among the pestivirus envelope proteins.

Amino Acid Sequence↗

In vitro and in vivo inhibition of nuclear type II estrogen binding sites in the dorsolateral prostate of noble rats.

Competition analyses with a number of known bioflavonoids and related compounds revealed that three of them competed effectively for type II [3H]estradiol- 17 beta ([3H]E2) binding sites (type II sites) in the nuclei of rat dorsolateral prostate (DLP). Amongst the bioflavonoids tested, quercetin was the most effect, exhibiting approx. a 50% inhibition at 3000-fold molar excess concentration. In contrast, rutin and hesperitin were both not effective. Methyl p-hydroxyphenyllactate (MeHPLA), a suspected "endogenous" ligand for uterine type II sites [1; J. Biol. Chem. 263, 1988, 7203-7210], competed as well as estradiol-17 beta (E2) for prostatic type II sites (50% inhibition at 30-fold molar excess), whereas its demethylated product, HPLA, did not. 4,4'Dihydroxybenzylidene acetophenone, an esterase-stable MeHPLA analog, was also found to be a good competitor, exhibiting a 50% inhibition at 100-fold molar excess concentration. In a preliminary in vivo study, quercetin, administered either orally or subcutaneously, was found to be effective in preventing a joint testosterone (T) and E2 treatment-induced elevation of type II sites in rat DLP. Quercetin treatments also caused a small but significant reduction (17-18%) in DLP relative gland weights (gland wt/body wt) in T + E2-treated animals. Taken together, these data suggest that bioflavonoids and related compounds may influence prostatic function via interactions with prostatic type II sites.

Animals↗

Effect of maximizing oxygen delivery on morbidity and mortality rates in critically ill patients: a prospective, randomized, controlled study.

OBJECTIVE: To determine the effects of optimizing oxygen delivery (DO2) to "supranormal" levels on morbidity and mortality in patients with sepsis, septic shock, and adult respiratory distress syndrome. DESIGN: A prospective, randomized, controlled trial. SETTING: A 16-bed surgical intensive care unit (ICU) and 14-bed mixed medical/surgical ICU in two separate hospitals in the University of Hawaii Surgical and Internal Medicine Residency programs. PATIENTS: During a 1-yr period, 67 patients who had pulmonary artery catheters and who met the criteria for sepsis or septic shock, adult respiratory distress syndrome, or hypovolemic shock were enrolled in the study. Patients admitted to the ICU who were < 18 yrs old, or with a do-not-resuscitate order, or those patients who faced imminent death (< 24 hrs), such as those patients with uncontrollable hemorrhage or brain death, were excluded from the study. INTERVENTIONS: Patients were randomized into treatment and control groups. The treatment group was assigned a therapeutic DO2 indexed (DO2I) goal of > 600 mL/min/m2. Interventions to attain this goal included fluid boluses, administration of blood products, and the use of inotropes. The control group was not assigned to a specific therapeutic goal other than "normal" values of DO2I of 450 to 550 mL/min/m2. Every attempt was made to reach the therapeutic goals within the first 24 hrs after entry into the study. Hemodynamic measurements were obtained on study patients every 4 hrs until the end of the study. The severity of illness was evaluated using the Therapeutic Intervention Scoring System, and the Acute Physiology and Chronic Health Evaluation II scoring system. MEASUREMENTS AND MAIN RESULTS: There were 32 patients in the control group and 35 patients in the treatment group. The groups were similar in age, sex, number of organ dysfunctions, Acute Physiology and Chronic Health Evaluation II and Therapeutic Intervention scores. There were no statistical differences between the two groups in mortality, development of organ failure, ICU days, and hospital days. Upon analysis, it became apparent that the patients comprised clinically distinct subgroups, including: a) a treatment group who achieved supranormal DO2I; b) a control group with normal DO2I; c) a treatment group who failed to reach target DO2I; d) a control group who self-generated to high DO2I values; and e) a small number of patients who could not even reach a normal DO2I of 450 mL/min/m2. These subgroups were found to be similar and matched. The mortality rate was significantly lower for patients in groups who reached supranormal values of DO2I whether treated or self-generated as compared with patients who reached normal DO2I values (14% vs. 56%, p = .01). CONCLUSIONS: Although there was no statistically significant difference in the control vs. treatment groups, subgroup analysis demonstrated a strong, significant difference between patients with supranormal values of oxygen transport vs. patients with normal levels of DO2. Supranormal values of DO2I, whether self-generated or as a result of treatment, resulted in a statistically significant decrease in mortality rate. This study adds to the weight of evidence that current standard of care of treating critically ill patients to normal DO2I should be reconsidered, and that maximizing to high DO2I might be a more appropriate therapeutic end-point.

Adult↗

A double-blind, prospective, randomized trial of ketoconazole, a thromboxane synthetase inhibitor, in the prophylaxis of the adult respiratory distress syndrome.

OBJECTIVE: To determine if ketoconazole, a thromboxane A2 synthetase inhibitor, given within the first 24 hrs after diagnosis and arrival in the intensive care unit (ICU) would decrease the frequency of adult respiratory distress syndrome in the septic patient population. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Twelve-bed, surgical ICU in a university-affiliated hospital. PATIENTS: Fifty-four consecutive patients admitted to the surgical ICU with the diagnosis of sepsis composed the study sample. Sepsis was defined as including two or more of the following signs in a patient with a systolic blood pressure of < 80 mm Hg or a systemic vascular resistance of < 800 dyne.sec/cm5: a) temperature > or = 39 degrees C or < or = 35 degrees C; b) white blood cell count of > 12,000 leukocytes, or < or = 4000 leukocytes/microL, or > or = 20% immature cells; c) positive blood culture; d) known or strongly suspected source of infection from which a known pathogen was cultured. INTERVENTIONS: Patients were randomized to receive either ketoconazole (400 mg) or placebo in a double-blind fashion as early as possible and in < 24 hrs after surgical ICU admission or after the diagnosis of sepsis was established. MEASUREMENTS AND MAIN RESULTS: Adult respiratory distress syndrome (ARDS) was diagnosed if the following criteria were met: a) intrapulmonary shunt of > 20%, or a PaO2/FIO2 ratio of < 150 requiring ventilatory support for > 48 hrs; b) pulmonary artery occlusion pressure of < 18 mm Hg and no clinical signs of heart failure; and c) diffuse infiltrates on chest radiograph. Treatment resulted in significant (p = .002) reduction in the frequency of ARDS compared with the placebo group, 64% vs. 15% in the ketoconazole treated group. The mortality rate was also reduced from 39% in the placebo group to 15% in the ketoconazole group (p = .05). A statistically significant reduction in ventilator and ICU days was not achieved. CONCLUSIONS: Ketoconazole (400 mg through the gastrointestinal tract) given early in the septic course may prevent ARDS and decrease the mortality rate in high-risk, septic patients.

Adult↗

ACh release from horse airway cholinergic nerves: effects of stimulation intensity and muscle preload.

This study was conducted to determine the effects of stimulation parameters and muscle preload on acetylcholine (ACh) release induced by electrical field stimulation (EFS) of horse airway cholinergic nerves. Trachealis strip bundles were prepared and suspended in 2-ml tissue baths. The tissues were stimulated three to five times for 30 min each. Increasing frequency (0.5-16 Hz) and voltage (5-20 V) increased ACh release; increasing pulse duration (0.5-3 ms) had only a minor effect. Alterations in muscle preload (2-20 g) had no effect on ACh release. ACh release was fairly constant for up to five repeated stimulation periods with the same EFS parameters. Stimulation of the tissues for 15 min released the same amount of ACh as 30 min if the amount was expressed as picomoles per gram per minute, suggesting that ACh release rate was constant during the 30-min period of stimulation. Atropine (10(-6) M) potentiated the release of ACh four- to fivefold, presumably by removing the autoinhibitory effect of ACh on the cholinergic nerves. Tetrodotoxin (10(-6) M) abolished the EFS-induced ACh release.

Acetylcholine↗

Prejunctional alpha 2-adrenoceptors inhibit acetylcholine release from cholinergic nerves in equine airways.

To determine the presence and function of alpha 2-adrenoceptors on cholinergic nerves innervating horse airway smooth muscle, the effects of some alpha 2-adrenoceptor agents on contractions of and acetylcholine (ACh) release from equine airway smooth muscle preparations were studied. Muscle contractions were elicited by either electrical field stimulation (EFS) or exogenous ACh. ACh release was induced by EFS and measured by high-pressure liquid chromatography and electrochemical detection. The alpha 2-adrenoceptor agonists clonidine (10(-7) to 10(-5) M) and UK-14,304 (10(-8) to 10(-6) M) concentration dependently inhibited ACh release and the contractile response to EFS but not the response to exogenous ACh. This inhibition was attenuated by the alpha 2-adrenoceptor antagonists yohimbine and idazoxan but not by the alpha 1-adrenoceptor antagonist prazosin. These results indicate that alpha 2-adrenoceptors exist on cholinergic nerves innervating equine airway smooth muscle, and activation of these receptors inhibits cholinergic neurotransmission. The observation that yohimbine alone had little effect on the contractile response to EFS suggests that, under these experimental conditions, endogenous norepinephrine had no influence on tracheal cholinergic neurotransmission via prejunctional alpha 2-adrenoceptors.

Acetylcholine↗

Presence of a specific antiestrogen binding site on human follicular thyroid carcinoma cell line (UCLA RO 82 W-1): inhibition by an endogenous ligand present in human serum.

A receptor for antiestrogens, distinct from the estrogen receptor, has been identified in several tissues including the MCF-7 breast cancer cell line. Estrogen receptors have also been found in normal and pathological thyroid tissue homogenates. We demonstrate the presence of an antiestrogen binding site (AEBS) on a pure human follicular thyroid carcinoma cell line (UCLA RO 82 W-1) using a 3H-tamoxifen (3H-TAM) binding assay. The binding of 3H-TAM to the AEBS was determined after preincubation (30 min) of the cells with excess 17 beta-estradiol (2 mumol/L). Specific and saturable binding of 3H-TAM to the cells was observed. Displacement of the tracer from its binding site was dose dependent. Scatchard analysis revealed a dissociation constant (Kd) of 73 nmol/L, indicating a binding site with moderate affinity and capacity (72 pmol/10(6) cells). Using this assay we were also able to demonstrate the presence of an endogenous ligand for the AEBS in ethanol extracts of human serum. Cell growth and 3H-thymidine incorporation by the follicular thyroid carcinoma cells were inhibited when the cells were exposed to TAM (1.5 mumol/L). In conclusion, TAM is able to bind to a specific receptor on this follicular thyroid carcinoma cell line, and a natural circulating ligand present in ethanol extracts of human serum interferes with its binding.

Adenocarcinoma, Follicular↗

[IgG RF analysis of synovial fluid of the knee joints in 35 patients with rheumatic disease].

Rheumatoid arthritis (RA) is an autoimmune disease. IgG RF in the synovial fluid is a significant indicator for the pathogenesis and differential diagnosis of this disease. To now, RF tested by latex agglutination belongs to the IgM type whereas, in the rheumatoid synovial fluid, most of immunocomplex molecules are IgG which bind into a complex. IgG RF was determined by ELISA in the synovial fluid of 35 cases of joint disorders, including 12 cases of RA, 7 cases of reactive arthritis (ReA), 5 cases of osteoarthritis (OA) and 11 cases of non-synovitis (non-S) which were regarded as negative control. The upper limit of OD value +2s was 0.5. Using this standard 7 out of 12 cases of RA were positive. 2 of 5 cases of OA were weakly positive, and only one case of ReA was positive. This suggest that this test is valuable in the diagnosis of RA. We have also observed the relation between IgG RF in synovial fluid and X-ray and arthroscopic findings of the same knee joint. In 5 of 7 cases of positive RA, II-III X-ray changes and II-III cartilage destruction arthroscopic findings were noted, suggesting a relationship between IgG RF in synovial fluid and articular damage.

Adolescent↗

Early alterations in ras protooncogene mRNA expression in testosterone and estradiol-17 beta induced prostatic dysplasia of noble rats.

BACKGROUND: The simultaneous treatment of intact Noble rats with testosterone and estradiol-17 beta for 16 weeks consistently induces intraductal dysplasia exclusively in the dorsolateral lobe (DLP) of the prostate. The lesion closely resembles human prostatic dysplasia and is considered to be a preneoplastic alteration, since invasive carcinoma frequently develop after long-term treatment of rats with both steroids. In our current study, we investigated steady-state ras transcript expression at the earliest recognized stages of sex steroid-induced dysplasia in the DLP. Our interest in studying ras expression in these evolving lesions stems from the pivotal role this family of genes are thought to play in the regulation of cell division and differentiation as well as in the genesis of a variety of human and animal neoplasms. EXPERIMENTAL DESIGN: Northern blotting and in situ hybridization were used to study ras protooncogene mRNA expression in the DLPs of NBL rats harboring sex steroid-induced ductal dysplasia and to compare findings with those from prostates of castrated and castrated androgen-treated animals. Since the prostate is an androgen-dependent gland, alterations in ras expression were compared with changes in the transcript levels of two androgen-responsive genes that encode for a prostatic secretory protein, seminal vesicle secretion protein II, and the androgen receptor. RESULTS: Similar to the situation for androgen receptor expression, orchiectomy initially enhanced levels of both H- and K-ras transcripts, whereas T administration to castrates was found to return the values to levels found in intact rats. Sixteen weeks of T and E2 administration to intact rats caused levels of H-ras mRNA and a 2.4 kb K-ras transcript to rise by 50 and 60%, respectively in the DLPs with dysplasia when compared with counterpart lobes from untreated control animals. In situ hybridization revealed markedly enhanced H-ras expression in some dysplastic DLP foci and no changes in histologically normal ducts and acini. CONCLUSIONS: Taken together, results from our studies suggest that the enhanced focal expression of ras protooncogenes may participate in early aberrant proliferation of prostatic ductal cells of the DLP. Early alterations of ras expression in dysplastic lesions may therefore be a key contributing event in the multistage development of prostate cancer in this animal model.

Animals↗

Preoperative intensive care unit consultations: accurate and effective.

OBJECTIVES: To determine if a structured preoperative ICU consultation would correctly assign patients to preoperative invasive monitoring, postoperative ICU care, or recovery room care, and to compare morbidity, mortality, and resource utilization among all groups. DESIGN: Prospective, observational study. SETTING: A university hospital. PATIENTS: A total of 475 patients who were referred preoperatively by surgeons for ICU consultation and were evaluated by ICU physicians. INTERVENTIONS: Patients assessed to have clinical evidence of cardiovascular compromise were admitted preoperatively to the ICU for invasive hemodynamic monitoring and optimization. Patients without such evidence, but who were to undergo major operations or had anticipated major fluid replacement were independently selected for invasive monitoring by anesthesiologists. Patients who developed physiologic instability or became unstable due to hemorrhage also underwent invasive monitoring. Nonmonitored patients who remained stable were given postoperative ICU care or went to the recovery room based on an assessment by the surgeon and anesthesiologist at the end of the operation. MEASUREMENTS AND MAIN RESULTS: Of 8,916 elective surgical cases, ICU physicians were consulted in 475 (5.3%) patients preoperatively. Sixty-seven patients were admitted preoperatively to the ICU for invasive hemodynamic monitoring and optimization; 60 patients had surgery (0.7% of elective cases, 12.6% of ICU consultations). Patients selected for ICU preoperative monitoring were older than non-monitored patients and had higher numbers of cardiovascular and total risk factors than any other group. They had higher Acute Physiology and Chronic Health Evaluation (APACHE II) scores, higher Therapeutic Intervention Scoring System (TISS) points, a higher number of complications, and longer ICU stays than non-monitored postoperative ICU patients. In addition, they had a higher number of complications than nonmonitored recovery room patients. APACHE II scores, TISS points, number of complications, and ICU days in the preoperative ICU admission group were not increased when compared with all other monitored patients. Neither hospital days nor total hospital charges were increased when compared with the other elective ICU patients. Patients selected for ICU preoperative monitoring who underwent surgery had an 11.7% mortality rate and accounted for four of five cardiovascular-related deaths. CONCLUSIONS: A small number of high-risk patients can be selected for preoperative monitoring on the basis of clinical assessment without increasing ICU stay or hospital bills. A structured preoperative consultation correctly identifies those patients who need monitoring and ICU care, but does not overutilize scarce and expensive ICU beds.

Aged↗

UV photoelectron and theoretical characterization of 2'-deoxyguanosine-5'-phosphate valence electronic properties: changes in structure associated with the B to Z-DNA conformational transition.

He(I) UV photoelectron spectroscopy and ab initio SCF molecular orbital calculations with the 4-31G basis set have been employed to characterize the valence electronic structures of 2'-deoxyguanosine-5'-phosphate (5'-dGMP-). In 5'-dGMP-, the electron distributions of the upper occupied orbitals are localized and similar to those appearing in 1,9-dimethylguanine (1), 3-hydroxytetrahydrofuran (2) and CH3HPO4- (3). Theoretical ionization potentials (IP's) of 5'-dGMP- (4) have been obtained by applying Koopmans' Theorem to the 4-31G SCF results. The IP's of seven orbitals in the base and sugar groups in 4, predicted from the 4-31G SCF calculations, have been individually corrected by comparison to results from 4-31G SCF calculations on neutral 5'-dGMP, and to Hel photoelectron spectra of the model compounds, 1 and 2. The IP's of six of the highest occupied orbitals of the phosphate group in 4 and in the model anion 3, predicted from 4-31G SCF calculations, have been corrected by comparing 4-31G SCF results for PO2- to theoretical IP's obtained from second-order Møller-Plesset perturbation calculations on PO2-. For 4 in the conformation occurring in B-DNA, the first IP's associated with the phosphate, base, and sugar groups occur at 5.1, 5.6 and 6.6 eV, respectively. A comparison of the valence electronic structures of 4 in geometries associated with the B and Z-DNA conformations indicates that in B-DNA the base and sugar orbitals have lower IP's than in Z-DNA, while the phosphate orbitals have higher IP's.

DNA↗

Construction of a dominant selectable marker using a novel dihydrofolate reductase.

Simian virus 40 promoter-enhancer-based mammalian expression plasmids using dihydrofolate reductase (DHFR)-encoding cDNA sequences originally isolated from two methotrexate (MTX)-resistant, DHFR-overproducing Chinese hamster lung cell lines were constructed. One, designated pSVA75, contains a DHFR cDNA that encodes leucine (Leu22) and corresponds to the wild type (wt), MTX-sensitive form of the enzyme [Melera et al., J. Biol. Chem. 263 (1988) 1978-1990]. The other plasmid, pSVA3, contains a cDNA that encodes a novel mutant form of the enzyme in which Leu22 has been changed to Phe [Melera et al., Mol. Cell Biol. 4 (1984) 38-48]. The resulting DHFR displays a 20-fold-enhanced resistance to inhibition by MTX, but maintains the catalytic activity of the wt enzyme [Albrecht et al., Cancer Res. 32 (1972) 1539-1546]. Transfection of DHFR- Chinese hamster ovary cells with either plasmid demonstrated that both were able to reconstitute the DHFR+ phenotype with equal efficiency (i.e., greater than 2.5 x 10(-3), indicating that both the wt and mutant enzymes were catalytically active in transfected cells. In addition, the mutant form of the enzyme was found to act as a dominant selectable marker when transfected into diploid DHFR+ cells, and to allow selection of resistant clones at low MTX concentrations (125 nM MTX) with a frequency of greater than 8 x 10(-4). Moreover, transfected clones were found to amplify their exogenous DHFR sequences to reasonably high levels (42-fold) at relatively low (888 nM) MTX concentrations, suggesting that substantial amplification of DHFR DNA and cotransfected sequences as well, can be achieved with this vector.

Animals↗

Nucleotide sequence of the genome of the filamentous bacteriophage I2-2: module evolution of the filamentous phage genome.

The nucleotide sequence of the circular single-stranded genome of the filamentous Escherichia coli phage I2-2 has been determined and compared with those of the filamentous E. coli phages Ff(M13, fl, or fd) and IKe. The I2-2 DNA sequence comprises 6744 nucleotides; 139 nucleotides less than that of the N- and I2-plasmid-specific phage IKe, and 337 (336) nucleotides more than that of the F-plasmid-specific phage Ff. Nucleotide sequence comparisons have indicated that I2-2, IKe, and Ff have a similar genetic organization, and that the genomes of I2-2 and IKe are evolutionarily more closely related than those of I2-2 and Ff. The studies have further demonstrated that the I2-2 genome is a composite replicon, composed of only two-thirds of the ancestral genome of IKe. Only a contiguous I2-2 DNA sequence of 4615 nucleotides encompassing not only the coat protein and phage assembly genes, but also the signal required for efficient phage morphogenesis, was found to be significantly homologous to sequences in the genomes of IKe and Ff. No homology was observed between the consecutive DNA sequence that contains the origins for viral and complementary strand replication and the replication genes. Although other explanations cannot be ruled out, our data strongly suggest that the ancestor filamentous phage genome of phages I2-2 and IKe has exchanged its replication module during evolution with that of another replicon, e.g., a plasmid that also replicates via the so-called rolling circle mechanism.

Amino Acid Sequence↗

Muscarinic receptor subtypes in equine tracheal smooth muscle.

Selective muscarinic receptor antagonists were used to identify muscarinic receptor subtypes in equine trachealis strips. The M1 receptor antagonist pirenzepine (10(-7) mol/L to 3 x 10(-5) mol/L) and the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 10(-9) mol/L to 3 x 10(-7) mol/L3) dose dependently inhibited the contractile responses to electrical field stimulation (EFS) and exogenous acetylcholine (ACh). Schild plots yielded a pA2 value for pirenzepine vs ACh of 6.75 +/- 0.09, which is consistent with the affinity for M2 or M3 receptors, and a pA2 value for 4-DAMP vs ACh of 8.47 +/- 0.09, which is in agreement with the affinity for M3 receptors. The M2 receptor antagonist gallamine (10(-5) mol/L and 10(-4) mol/L) did not affect the response of trachealis to exogenous ACh and low-frequency EFS (0.1-2 Hz) but decreased the responses to high-frequency EFS (4-16 Hz). These results suggest that the muscarinic receptors mediating contractions induced by ACh in equine tracheal smooth muscle are of the M3 subtype. The lack of an increase in the response to EFS following gallamine suggests that functional prejunctional inhibitory M2 receptors are not present on the cholinergic nerves innervating equine tracheal smooth muscle.

Acetylcholine↗

Exogenous but not endogenous PGE2 modulates pony tracheal smooth muscle contractions.

The modulatory role of prostaglandin E2 (PGE2) was examined in pony tracheal smooth muscle strips. Although exogenous PGE2 inhibited the contractile response to both electrical field stimulation (EFS) and acetylcholine (ACh) in a dose-dependent manner, the concentration required to inhibit the response to EFS (10 nM) was less than that required to inhibit the response to ACh (0.1 microM). Cyclooxygenase inhibition with aspirin or meclofenamate had no effect on either the response to EFS or to ACh even though PGE2 production was inhibited. Our results demonstrate that in ponies as in other species, exogenous PGE2 can inhibit the airway smooth muscle's response to EFS and ACh. However, the failure of cyclooxygenase inhibition to alter the response to EFS and ACh suggests that endogenous prostanoids do not exert a significant modulatory effect on pony tracheal smooth muscle in vitro.

Acetylcholine↗