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SUMMARY

Effects induced by long-term administration of clenbuterol at anabolic dosages (20 µg/kg of body weight for 40 days) on β-adrenergic receptor (β-ar) subtypes, estrogen receptors (er), and progesterone receptors (PgR) in the reproductive system of female veal calves were investigated. Clenbuterol treatment induced a significant (P < 0.01) down-regulation of β-ar subtypes (β1-ar, β2-ar, myometrial high-affinity β2-ar, and ovarian low-affinity β2-ar). On the other hand, a significant (P < 0.01) increase of uterine and ovarian er and PgR receptors was observed in treated calves. Treatment did not affect dissociation constant values of β-ar, er, or PgR. In similar manner, clenbuterol did not significantly modify distribution of er and PgR in the various tissues of the genital tract. In fact, these receptors were significantly (P < 0.05) more concentrated in the uterus than in the vagina in treated and untreated calves. Data indicated that prolonged clenbuterol exposure induced homologous β-ar down-regulation (down-regulation of its specific receptors) and heterologous er and PgR up-regulation (up-regulation of different types of receptors, not specifically bound by clenbuterol) in the genital tract of veal calves. Modification of the receptorial status could be reasonably related to the pathologic changes observed in long-term treated calves (eg, hydrometra, dilatation of uterine glands, cystic ovaries). The increased concentrations of er and PgR suggested the possible existence of subcellular mechanisms regulated by repeated β-adrenergic stimulation.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the concentration and binding characteristics of α-adrenoceptor subtypes in smooth muscle cell membranes of equine ileum.

Sample Population—Segments of longitudinal and circular smooth muscle from the ileum of 8 male and 8 female adult horses.

Procedure—Distribution of α-adrenoceptor subtypes was assessed by use of radioligand binding assays incorporating [3H]-prazosin and [3H]-rauwolscine, highly selective α1- and α2-adrenoceptor antagonists, respectively. Characterization of adrenoceptor subtypes was performed by use of binding inhibition assays.

Results—On the basis of binding affinity for specific radioligands, low- and high-affinity α1- and α2-adrenoceptors were detected. Concentration of low-affinity α2-adrenoceptors was significantly greater in male horses, compared with females. Competition studies confirmed the specificity of the radioligands used in the binding assays. α1-Adrenoceptors of both subtypes in male and female horses had a higher affinity for prazosin than phentolamine, whereas yohimbine did not compete with the radioligand for binding. For α2-adrenoceptors regardless of subtype, potency of inhibition elicited by each drug varied between sexes. In males, yohimbine was a more potent inhibitor than phentolamine, which was more potent than prazosin. In females, yohimbine was more potent than prazosin, which was more potent than phentolamine.

Conclusions and Clinical Relevance—High- and low-affinity α1- and α2-adrenoceptors were detected in smooth muscle of equine ileum. Because α-adrenoceptor subtypes, particularly α2-adrenoceptors, are involved in the regulation of gastrointestinal tract function, characterization of these receptors may represent the basis for development of new therapeutic strategies for the control of gastrointestinal disturbances in horses. (Am J Vet Res 2001;62:1370–1374)

Full access
in American Journal of Veterinary Research

SUMMARY

The toxicity of zinc ethylene-bis-dithiocarbamate (zineb), a widely used fungicide, was studied in four 4-week-old Friesian calves with immature rumen function. Calves were first subjected to liver biopsy, and thereafter, 3 of them were orally administered 200 mg of zineb/kg of body weight daily for 80 days, whereas the fourth calf served as control and remained untreated. Clinical, hematologic, and pathologic (including ultrastructural) findings were recorded. The distribution in body fluids and tissues of the parent compound and one of its main metabolites, ethylenethiourea (etu), also was examined. Treated calves had unthrifty appearance and reduction in weight gain. They also had remarkable impairment of thyroid function, as reflected by reduction in serum concentrations of triiodothyronine and thyroxine and increase in weight of the thyroid gland associated with epithelial vacuolization and foci of hyperplasia. Moderate increase in liver glycogen content and impairment in maturation of germ cells were recorded consistently. Whereas zineb was widely distributed in body tissues, etu accumulated mainly in the liver and the thyroid gland, although noticeable concentrations also were attained in muscle. Data were consistent with involvement of etu mainly in the pathogenesis of thyroid gland lesions, and indicate that unweaned calves given zineb develop a clinicopathologic syndrome that does not differ qualitatively from that already described in adult cattle exposed to zineb.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To identify β-adrenergic receptor subtypes in ileum smooth muscle of the horse.

Sample Population

Isolated strips of equine longitudinal ileum smooth muscle and membrane preparations from smooth muscle of the intestinal wall.

Procedure

Functional assays and radioligand binding assays.

Results

Relaxation of ileum longitudinal smooth muscle proved to be mainly caused by stimulation of β-atypical and β2-adrenergic receptors. Binding studies on cell membranes indicated that the total β-adrenergic receptors population consists of 54% β-atypical, 34% β2-, and 12% β1-subtypes.

Conclusions

The data suggest that sympathetic relaxation of equine ileum smooth muscle depends mainly on β-atypical receptor subtypes activation, with a minor contribution by β2-subtypes.

Clinical Relevance

The important role of β-atypical adrenergic receptor subtypes in the relaxation of equine ileum suggests possible clinical use of selective β-atypical receptor agonists to control intestinal disturbances. (Am J Vet Res 1997;58:621–625)

Free access
in American Journal of Veterinary Research

SUMMARY

Objective

To identify β-adrenoceptor subtypes involved in motility inhibition of circular and longitudinal smooth muscle layers of equine ileum.

Sample Population

Isolated strips of equine ileum circular smooth muscle and membrane preparations from circular and longitudinal muscle layers.

Procedure

Functional assays of circular muscle preparations and radioligand binding assays and measurements of cAMP production in smooth muscle membranes from circular and longitudinal layers.

Results

Selective β-adrenergic agonists exerted inhibitory effects on circular muscle preparations. Binding studies of cell membranes indicated that the density and distribution of 3 β-adrenoceptor subtypes did not differ between longitudinal and circular muscle layers. Measurement of cAMP production in membrane preparations of longitudinal and circular muscle after selective β-stimulation confirmed presence of the 3 adenylate cyclase-coupled β-adrenoceptor subtypes; however, preparations from the 2 layers had differing cAMP production efficacy.

Conclusions

The data may partly explain the differing functional responses between circular and longitudinal muscle preparations.

Clinical Relevance

Findings support the important role of β-atypical adrenoceptors in the inhibitory regulation of equine ileum motility. (Am J Vet Res 1997;58:1422–1426)

Free access
in American Journal of Veterinary Research

SUMMARY

Female Sprague-Dawley rats were treated IM with 0, 2.5, 25, and 50 μg of clenbuterol HCl/kg of body weight/d for 21 days. In all treated rats, significant increase in body weight gain (P < 0.05) and improvement in feed conversion ratio (P < 0.05) were recorded. Hydrometra was observed in the uterus of treated rats, and histologically, it was possible to see dilatation of luminal glands and ovarian alterations. Clenbuterol treatment induced significant (P < 0.05) increase in uterine estrogen receptor concentration of rats treated with the 2 higher doses. Treatment apparently failed to enhance the rate of oxidative and conjugative biotransformations, except for glucuronidation of p-nitrophenol (P < 0.05). On the basis of the data obtained, we could affirm that high doses of clenbuterol affect the female reproductive system of rats inducing, almost in part, estrogen-like modifications, but probably by a different mechanism of action correlated to intense adrenergic stimulation.

Free access
in American Journal of Veterinary Research