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PubMed1987

The effect of vasoactive intestinal peptide on smooth muscle tone and mucus secretion from the ferret trachea.

The effect of vasoactive intestinal peptide (VIP) was examined on the smooth muscle contraction and mucus secretion produced by methacholine and phenylephrine in the ferret whole trachea in vitro. VIP (0.5 to 800 nM) produced a concentration-dependent relaxation of the ferret trachea contracted by methacholine (1 microM) and phenylephrine (10 microM). The concentration-response curves for methacholine- and phenylephrine-induced contractions were both shifted to the right by VIP (0.1 microM). Methacholine-induced secretion was inhibited in a concentration-dependent manner by VIP, whereas that due to phenylephrine was enhanced. The concentration-response curve for methacholine-induced secretion was shifted to the right by VIP, whereas the curve for phenylephrine was shifted to the left. Methacholine produced a concentration-dependent increase in the rate of output of lysozyme from the ferret trachea with no corresponding increase in the concentration of lysozyme in the mucus. Phenylephrine produced a concentration-dependent increase in the rate of output and in the concentration of lysozyme. VIP (0.1 microM) significantly increased the concentration of lysozyme in the mucus produced by methacholine with no increase in the rate of lysozyme output. However, the rate of lysozyme output due to phenylephrine was significantly increased by VIP (0.1 microM) with no increase in concentration. We suggest that VIP inhibits secretion from mucous cells stimulated by methacholine, and enhances the secretion produced by phenylephrine from serous cells.

Animals↗
PubMed1989

Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor.

1. The effects of substance P (SP) and neurokinin A (NKA) were examined on tracheal smooth muscle tone, mucus volume output, lysozyme output and albumin transport across the ferret in vitro whole trachea in the presence and absence of the enkephalinase inhibitor, thiorphan. 2. SP (0.001-3 microM) and NKA (0.01-10 microM) contracted the tracheal smooth muscle and increased mucus volume, lysozyme and albumin outputs into the tracheal lumen. The EC50 values for SP and NKA for all of the variables measured were significantly reduced, and all of the maximum responses were significantly enhanced by thiorphan (10 microM). 3. In the presence of thiorphan, SP (1 microM) and NKA (10 microM) produced albumin concentrations in the secreted mucus (8.9 and 7.2 micrograms microliters-1) which were greater than those in the submucosal buffer (4.2 micrograms microliters-1). 4. In the presence of thiorphan, NKA was approximately 5 times more potent than SP at contracting the tracheal smooth muscle. Conversely SP was 23, 15 and 22 times more potent than NKA at stimulating mucus volume, lysozyme and albumin outputs respectively. 5. Thus, there is neutral endopeptidase in the ferret trachea in vitro which cleaves exogenously applied SP and NKA, thereby reducing the magnitude and potency of their actions. SP and NKA contract the ferret tracheal muscle probably by an action at NK2 (or NK3)-receptors but stimulate mucus volume output, lysozyme output and albumin transport across the tracheal wall probably by an action on NK1 receptors.

Animals↗
PubMed1991

5-HT3 receptor agonism may be responsible for the emetic effects of zacopride in the ferret.

The racemic 5-HT3 receptor antagonist, zacopride (10-100 micrograms kg-1, i.m.) evoked an emetic response in ferrets. This property appeared to reside totally in the S-enantiomer which also produced emesis over the same dose range. This emesis could be prevented by pretreatment with ondansetron (1 mg kg-1, i.m.) or by R-zacopride (100 micrograms kg-1, i.m.). In urethane-anaesthetized ferrets, S-zacopride (0.3 micrograms kg-1, i.v.) evoked a profound Bezold-Jarisch reflex which was blocked by both ondansetron (30 micrograms kg-1, i.v.) and by R-zacopride (100 micrograms kg-1, i.v.). These results suggest that, in the ferret, S-zacopride possesses 5-HT3 receptor agonist properties which may be responsible for the emetic effect. In contrast R-zacopride does not appear to possess 5-HT3 receptor agonist properties in this species.

Anesthesia↗
PubMed1992

Platelet-activating factor relaxes ferret tracheal smooth muscle and reduces transepithelial potential difference in vitro.

1. The effects of platelet activating factor (PAF) were examined on the smooth muscle tone, mucus volume, lysozyme and albumin outputs and potential difference (PD) across the ferret tracheal wall. 2. PAF (0.1-10 microM) had no direct effect on mucus volume, lysozyme or albumin output from the ferret trachea. PAF produced concentration-dependent relaxations of the tracheal smooth muscle and reductions in PD across the tracheal wall. There was no change in the histological appearance of the trachea after exposure to PAF. 3. The PAF-induced smooth muscle relaxation was not affected by FPL55712, a combination of mepyramine and cimetidine, or by a combination of the oxygen free-radical scavengers catalase and superoxide dismutase (SOD); but was abolished by indomethacin or the PAF-receptor antagonist WEB2086. 4. The PAF-induced reduction in PD was not affected by indomethacin, FPL55712 or mepyramine and cimetidine, but was prevented by catalase and SOD, and by WEB2086. 5. We conclude that PAF relaxes ferret tracheal smooth muscle in vitro by receptor-mediated release of a bronchodilator prostaglandin, possibly PGE2. PAF also reduces PD across the trachea suggesting changes in epithelial function; however, there is no histological epithelial damage after PAF. The reduction in PD with PAF is probably produced by receptor-mediated release of oxygen free-radicals. The cellular source of these free-radicals and of the dilator prostaglandin is unclear.

Animals↗
PubMed1994

'Sensory-efferent' neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro.

1. We characterized the tachykinin receptor(s) mediating 'sensory-efferent' neural control of release of 35SO4-labelled macromolecules (mucus) from ferret trachea in vitro in Ussing chambers using selective tachykinin antagonists. Secretion was induced by substance P (SP), neurokinin A (NKA), capsaicin, the NK1 tachykinin receptor agonist [Sar9, Met(O2)11]substance P ([Sar9]SP), or acetylcholine (ACh), or by electrical stimulation of nerves. Antagonists used were FK888 and L-668,169, selective for the NK1 receptor, SR 48968, selective for the NK2 receptor, and FK224, a dual antagonist at NK1 and NK2 receptors. The selectivity of FK888 and SR 48968 was examined on NKA-induced contraction of ferret tracheal smooth muscle in vitro. 2. SP (1 microM) increased mucus secretion by 695% above vehicle controls. FK888 (0.1 microM-30 microM) inhibited SP-induced secretion in a dose-dependent manner, with complete inhibition at 10 microM and an IC50 of 1 microM. L-668,169 (1 microM) also completely inhibited SP-induced secretion. 3. NKA (1 microM) significantly increased mucus secretion by 271% above baseline, a response which was completely inhibited by FK888 (10 microM) or L-668,169 (microM). Secretion induced by ACh (10 microM: 317% above baseline) was not inhibited by FK888 but was inhibited by atropine. Capsaicin (10 microM)-induced secretion (456% above vehicle controls) was significantly inhibited by FK888 and by L-668,169 (111% and 103% inhibition respectively). 4. Electrical stimulation (50 V, 10 Hz, 0.5 ms, 5 min) increased mucus output above baseline (increased by 12 to 26 fold), a response blocked by tetrodotoxin (0.1 microM). FK888 (10 microM) inhibited the increase in secretion due to electrical stimulation by 47%. Atropine, propranolol and phentolamine in combination(APP) inhibited the response to electrical stimulation by 48%. The remaining NANC response, i.e. in the presence of APP, was further reduced by 66% with FK888. FK224 (10 microM) inhibited neurally evoked secretion by 73%. SR 48968 (0.1 fLM) had no effect on electrically-stimulated or [Sar9]SP-induced secretion.5. NKA (10nM- 1O microM: in the presence of DMSO control vehicle) induced tracheal smooth muscle contraction in a concentration-dependent manner with a maximal contraction of 30% of the maximal response to ACh (10 mM) and an ECm of 0.3 JAM. SR 48968 (0.1 microM in DMSO) inhibited the NKA induced contraction whereas FK888 did not. Neither antagonist had any inhibitory effect on ACh induced contraction.6. We conclude that 'sensory-efferent' neurogenic mucus secretion in ferret trachea in vitro is mediated via tachykinin NK, receptors with no involvement of NK2 receptors. Potent and selective tachykinin antagonists may have therapeutic potential in bronchial diseases such as asthma and chronic bronchitis in which neurogenic mucus hypersecretion may be aetiologically important.

Animals↗
PubMed1996

An interaction of ondansetron and dexamethasone antagonizing cisplatin-induced acute and delayed emesis in the ferret.

1. Cisplatin, 5 mg kg-1, i.p., administered as a single treatment, induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of ondansetron and dexamethasone and their interaction over a three day period. 2. Ondansetron, 1 mg kg-1, i.p., administered three times per day in two experiments, antagonized significantly the retching and vomiting that occurred on days 1 and 2 by 60-76 and 73-84%. On the third day of treatment there was a trend for a 38% reduction in one experiment and a 74% reduction in the other. 3. There was a trend for dexamethasone, 1 mg kg-1, i.p., administered as a single daily injection for three days, to reduce by 37% the retching and vomiting response that occurred on day 1, the reduction of 77% on day 2 achieved significance and dexamethasone non-significantly increased the retching and vomiting response by 46% on day 3. However, dexamethasone 1 mg kg-1 i.p. administered three times per day for three days significantly reduced the retching + vomiting response by 85, 97 and 86% on days 1, 2 and 3 respectively. 4. The combination of dexamethasone, 1 mg kg-1, i.p., as single daily injections with ondansetron, 1 mg kg-1, i.p., administered three times per day improved the control of the retching and vomiting response, significantly reducing the total numbers of retches and vomits by more than 70% over a three day period. The combination of dexamethasone (1.0 mg kg-1) and ondansetron (1.0 mg kg-1), both administered three times daily, abolished cisplatin-induced emesis over the three day period. 5. The three times per day administration of ondansetron, 1 mg kg-1, i.p., plus dexamethasone, 1 mg kg-1, i.p., administered only on day 1 prevented day 1 emesis but did not modify the retching and vomiting that occurred on days 2 and 3. 6. The present results indicate that ondansetron and dexamethasone significantly reduce cisplatin-induced emesis in the ferret during both the acute and delayed phase; drug/co-treatment can exert an additive action to abolish cisplatin-induced emesis. The ferret model may be useful to detect anti-emetic drug action for treatment of chemotherapy-induced acute and delayed emesis in man.

Animals↗
PubMed1986

The ferret: a new model of oral ethanol injury involving the liver, bone marrow, and peripheral blood lymphocytes.

We have developed a model of oral ethanol ingestion in the ferret by providing a complete liquid diet in which 21% of the total caloric intake is given as ethanol. After 3 weeks of ethanol treatment, migration inhibitory factor activity from ferret lymphocytes was significantly decreased when compared to animals fed a dextrose-substituted, identical liquid diet. Lymphocyte blastogenesis in response to the mitogen, phytohemagglutinin, was also decreased after 6 weeks of ethanol ingestion. Histopathologically, hepatic cell degeneration, fat deposition, and "Mallory body-like" material were present after 11 weeks of therapy. Bone marrow aspirate cells from the iliac crest of ethanol-fed animals showed vacuolization in both erythroid and myeloid elements after 6 weeks of ethanol ingestion. Mean ferret weights were not significantly different between the ethanol and dextrose control groups; serum ethanol and acetaldehyde concentrations were somewhat higher over the study period compared to those seen in human alcoholics. Therefore, we have designed a small animal model of the toxic effects of alcohol in which multiple organ systems exhibited evidence of ethanol-related disease.

Alcoholism↗
PubMed1996

The effect of cyclosporin-A on the oral microflora at gingival sulcus of the ferret.

The effect of cyclosporin-A (CyA) on the dentogingival flora of ferrets with healthy and experimentally induced periodontal breakdown was studied. Five animals were given 10 mg/kg/d CyA. At the start of the experiments (day 0), ligatures were placed around 4 teeth in the right upper and lower jaws; corresponding contralateral teeth on the left side served as control. On days 0 and 28 (end of the experiment), microbiological samples were collected from the gingival sulcus of the experimental and the control teeth and from closely located gingival mucosa membrane. The samples were subjected to viable counts and to darkfield microscopic analyses. On day 0, facultative anaerobic rods, mainly Pasteurella spp, Alcaligenes spp, Corynebacterium spp. and Rothia spp dominated in the viable counts. No anaerobic bacteria were detected in the viable counts. On day 28 spirochetes increased in the experimental gingival sulcus samples and anaerobic bacteria appeared in most of the samples and constituted 40-60% of the total cultivable flora; Fusobacterium necrophorum and Eubacterium spp. predominated in the samples from the experimental sites. The results of the present study were compared with those of our previous investigation of ferrets not medicated with cyclosporin but also subject to experimental ligature periodontitis. Eubacterium spp. were absent in the animals not treated with cyclosporin, while this species was frequently present in the immunosuppressed ferrets. The results indicate that the presence of the large numbers of gram negative rods and of anaerobic bacteria may have enhanced the inflammatory process and further provoked the gingival overgrowth observed.

Actinomycetaceae↗
PubMedDate not supplied

Adrenal ultrasonography correlated with histopathology in ferrets.

The adrenal glands of twenty-six, 12- to 53-month-old, ferrets without clinical signs of adrenal disease were examined and measured by ultrasonography and the findings compared with those from gross examination and histopathology. Of 51 adrenal glands examined, 27 were normal, 23 had either nodular or diffuse cortical hyperplasia and 1 had an adenocarcinoma. There was no statistically significant difference between the sonographic nor gross size of normal adrenal glands and those with hyperplasia. Moderate correlation was found between gross and sonographic measurements of length for both right (r = 0.783; p < 0.0001) and left (r = 0.609; p < 0.001) and width (p < 0.02). In female ferrets, the length, width, and depth of the right adrenal gland sonographically measured (mean +/- sd) 7.5 +/- 1.2 mm, 3.7 +/- 0.6 mm, 2.8 +/- 0.4 mm, respectively, and the left measured 7.4 +/- 1.0 mm, 3.7 +/- 0.4 mm, 2.8 +/- 0.4 mm; in males, the right adrenal measured 8.9 +/- 1.6 mm, 3.8 +/- 0.6 mm, 3.0 +/- 0.8 mm and the left measured 8.6 +/- 1.2 mm, 4.2 +/- 0.6 mm, 3.0 +/- 0.6 mm. Accessory adrenal tissue was not identified during the sonographic examination but was grossly found in 10 of the ferrets. It was associated with either the right, left or both adrenal glands.

Adenocarcinoma↗
PubMedDate not supplied

Bilateral perinephric pseudocysts and polycystic kidneys in a ferret.

A 3-year-old castrated male domestic ferret was evaluated for abdominal distention. Survey lateral and dorsoventral abdominal radiographs were made. There were two soft tissue radiopacities consistent with grossly enlarged kidneys displacing small bowel and colon cranially, ventrally and caudally. Abdominal ultrasound was performed and revealed bilateral perinephric pseudocysts and polycystic kidneys. The perinephric pseudocysts were found to be dilated renal capsules on exploratory surgery and were drained. On follow up examinations, the pseudocysts were drained by ultrasound-guided paracentesis. The perinephric cyst fluid was distinguished from urine by measuring creatinine concentration and plans were made to resect the renal capsules due to rapid re-accumulation of pseudocyst fluid. The ferret's condition deteriorated and euthanasia was performed. Post-mortem examination was declined by the owner. Perinephric pseudocysts are rare and this is the first published report in a ferret. Ultrasound examination is the most rapid, accurate and non-invasive method for diagnosis of perinephric pseudocysts.

Animals↗
PubMedDate not supplied

Radiographic measurement of cardiac size in normal ferrets.

Right lateral, left lateral and ventrodorsal radiographs were obtained in 20 normal ferrets (11 male). Three independent observers recorded measurements of the cardiac silhouette and results for each parameter were averaged. Long axis (length), short axis (width) and total of length plus width (L+W) were recorded in each view. Comparative measurements were calculated, including the ratio of L+W/length of thoracic vertebrae 5-8, and a modified vertebral heart score (VHS) method, measuring the heart in vertebral units. Measurements made in ventrodorsal views were usually larger than corresponding measurements in lateral views. Weight and most absolute measurements differed significantly between male and female ferret (P<0.05), but the differences in absolute measurements were not apparent when related to measures of body size (Ratio and modified VHS methods). Given the variability in body weight and size in ferrets, measurements of the cardiac silhouette normalized for body size may be more universally applicable than absolute measurements.

Age Factors↗
PubMed2004

Treatment of a prolapsed lumbar intervertebral disc in a ferret.

A seven-month-old, male ferret had acute paraplegia and radiographs showed signs of disc prolapse between the second and third lumbar vertebrae (L2/3). Hemilaminectomy was performed to decompress the spinal cord. Histological examination revealed that the extradural material was consistent with annulus fibrosus and the L2/3 articular facets were enlarged as a result of bone remodelling. The ferret became ambulatory one month postoperatively. Five months postoperatively, the ferret had normal posture with mild proprioceptive deficits in the pelvic limbs, and fusion of the L2 and L3 vertebral bodies.

Animals↗
PubMed2004

Two unusual tumours in a ferret (Mustela putorius furo).

This case report describes the clinical history, diagnosis and treatment of a ferret with a tumour of the right adrenal gland and insulinomas of the pancreas. Histopathology of both lesions confirmed the diagnoses. Clinical signs of the adrenal gland tumour were a swollen vulva, overgrooming, sexual activity and pruritus. The clinical signs suggesting insulinomas were collapse of the ferret, disorientation and ptyalism. A low blood glucose level assisted the diagnosis of insulinomas. This is believed to be the first reported case of concurrent insulinomas and adrenal gland tumour in a ferret in the United Kingdom.

Adenoma↗
PubMed2005

Thyroid follicular adenocarcinoma in a ferret.

A 5-year-old male castrated ferret was presented to the Washington State University College of Veterinary Medicine for evaluation of progressive hair loss and a large, rapidly growing ventral neck mass. The patient had been diagnosed previously with an insulinoma, which was managed medically. Fine-needle aspirates of the neck mass were performed. The cytologic results were most consistent with epithelial neoplasia, likely a carcinoma; thyroid origin was considered likely based on tumor location and cell morphology. The tumor grew rapidly, and the owners elected euthanasia 1 week after examination. At necropsy, a circumscribed, ovoid mass disrupted the right cervical musculature next to the right lobe of the thyroid gland. Histopathologic evaluation revealed an infiltrative mass consisting of cuboidal cells arranged in solid sheets and irregular follicles enclosing colloid. The cells were large, with prominent nucleoli, and had a high mitotic rate. The histopathologic diagnosis was consistent with thyroid follicular adenocarcinoma. Immunochemical findings confirmed thyroglobulin production by neoplastic cells, but to a lesser extent than in normal ferret thyroid tissue. To our knowledge, this is the first case of thyroid follicular adenocarcinoma to be reported in a ferret, with only 1 other case of thyroid carcinoma, a C-cell carcinoma, described previously.

Adenocarcinoma, Follicular↗
PubMed1981

The metabolism of bifluranol by rat, dog and ferret.

The synthesis of monohydroxy- and dihydroxy-bifluranol, and of glucuronide and sulphate conjugates of bifluranol are described. Bifluranol administered orally to rats, ferrets and dogs at a dosage of 50 to 200 microgram kg-1 is mostly excreted in the faeces as unchanged bifluranol and bifluranol monosulphate, disulphate and monoglucuronide. The bifluranol is well absorbed and is mostly excreted in the bile, as six different conjugates, including a glucuronide sulphate found in all 3 species, and a glucuronide phosphate found only in ferret and dog bile. Hydroxylation of the aromatic rings occurs in the rat, to an extent of about 8% of the dose, but was not detected in ferret or dog.

Animals↗
PubMed1985

Characteristics of the vagally driven non-adrenergic, non-cholinergic inhibitory innervation of ferret gastric corpus.

This paper reports a quantitative in vivo study on the vagal activation of the intramural non-adrenergic, non-cholinergic inhibitory nerves in the ferret gastric corpus. The nature of the inhibitory neurotransmitter was also investigated. In the atropinized, guanethidine-treated, urethane-anaesthetized ferret, electrical stimulation (10 s at 20 V, 1-20 Hz, 0.5 ms pulses) of the cervical vagi produced a prompt fall in intracorpus pressure that was related to the stimulus frequency. The maximal response was achieved at 10 Hz. The time taken for the intracorpus pressure to return to pre-stimulus levels after a 10 s period of stimulation was related to the stimulus frequency; at 10 Hz the pressure took approximately 11 min to recover. In contrast to studies in the cat (Martinson & Muren, 1963), there was no detectable difference in the electrical threshold for activation of the vagal excitatory and vagal inhibitory fibres. The nature of the vagal non-adrenergic, non-cholinergic inhibitory neurotransmitter was investigated using a variety of antagonists and agonists. Adenosine triphosphate (ATP), adenosine, alpha beta-methylene ATP and beta gamma-methylene ATP all contracted the corpus in the presence of vagotomy, atropine, guanethidine and indomethacin. The vagally induced fall in corpus pressure was not blocked by high doses of alpha beta-methylene ATP. A variety of peptides were investigated for their effects on corpus pressure in the presence of atropine, guanethidine and vagotomy. Bombesin, pentagastrin, substance P, cholecystokinin octapeptide (CCK-8) and bradykinin all produced an increase in intracorpus pressure. Neurotensin and vasoactive intestinal polypeptide (VIP) both decreased intracorpus pressure, and of the two VIP most closely mimicked the response to vagal activation of the non-cholinergic, non-adrenergic inhibitory neurones. The results provide support for the involvement of a peptide (possibly VIP) rather than a purine in the vagally driven decrease in intracorpus pressure in the ferret.

Adenosine Triphosphate↗
PubMed1987

The effects of calcium on potassium transport in ferret red cells.

1. The effects of changes in the concentration of intracellular calcium on potassium transport were investigated in ferret red cells. Bumetanide was used to divide potassium transport into three components: total, bumetanide sensitive and bumetanide resistant. The bumetanide-sensitive component is equivalent to sodium-potassium-chloride co-transport. 2. Internal calcium concentration was controlled with the ionophore A23187 which was present throughout the experiments. 3. Changes in internal ionized calcium over the range 5 X 10(-10) M to 7 X 10(-7) M did not affect any component of potassium uptake. 4. Increasing the internal ionized calcium concentration above 10(-6) M stimulated bumetanide-resistant potassium transport. Half-maximal stimulation of this system was achieved with 3 X 10(-6) M-internal calcium. The system spontaneously inactivated after the initial activation by calcium and ionophore. Transport was inhibited by 1 mM-quinine. 5. Increasing the internal ionized calcium concentration to 10(-5) M had no effect on bumetanide-sensitive transport. 6. Concentrations of intracellular ionized calcium above 10(-5) M inhibited all three components of transport. Inhibition of the bumetanide-sensitive component was only slightly reversed when internal calcium concentration was reduced to normal. 7. Physiological changes in internal ionized calcium concentration do not affect sodium-potassium-chloride co-transport in ferret red cells. Very high concentrations of calcium inhibit transport, probably by an indirect mechanism. 8. In the course of the experiments the concentration of ionized intracellular magnesium in oxygenated ferret red cells was found to be about 0.65 mM.

Animals↗
PubMed1989

Secretion of protein from salivary glands in the ferret in response to vasoactive intestinal peptide.

1. Secretory responses of ferret parotid and submandibular glands were investigated in the presence of muscarinic, alpha- and beta-adrenoceptor blocking agents. 2. In pentobarbitone-anaesthetized animals I.V. doses of vasoactive intestinal peptide (VIP) failed to elicit overt secretion of saliva from either gland. 3. However, an occult secretion of protein occurred in response to VIP from both types of gland. This was revealed by means of a subsequent I.V. wash-out injection of substance P, which is a potent secretagogue in ferrets. This effect of VIP was much more marked in the submandibular than in the parotid gland. 4. Electrical stimulation of the chorda-lingual nerve gave rise to protein secretion in the submandibular gland at subthreshold frequencies for overt non-cholinergic, non-adrenergic secretion of saliva, as revealed by subsequent wash-out I.V. injection of substance P. 5. Protein secretion in response to VIP was also demonstrated in vitro by perifusing small pieces of the two glands. The sensitivity of submandibular tissue to VIP greatly exceeded that of the parotid tissue. 6. It is concluded that VIP, or a structurally related peptide, may be involved in the non-cholinergic, non-adrenergic secretory response of ferret salivary glands evoked by parasympathetic nerve stimulation.

Animals↗