Effects of Inflammation upon beta-adrenoceptor concentrations in the common digital artery of the horse: an in vitro study.
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Adrenergic beta-Antagonists↗
Biomedical subjects
C Girardi
Publications and source records attributed to C Girardi.
Identification of functional alpha-adrenoceptor subtypes in the bovine female genital tract during different phases of the oestrous cycle.
The concentration and functionality of the alpha-adrenoceptor (alpha-AR) subtypes in the genital tract of cyclic heifers were investigated. In each tissue sample, a single class of alpha1-ARs was observed, whereas two distinct classes of alpha2-ARs were discriminated: low-affinity (LA) and high-affinity (HA) alpha2-ARs. Statistical analysis showed the presence of significantly (p < 0.05) higher concentrations of all alpha-AR subtypes in the follicle than in the corpus luteum. No significant differences were found in the ovary or myometrium between the luteal and follicular phases. In the ovary, the density of alpha1-ARs was significantly (p < 0.05) higher than that of alpha2-ARs. By contrast, there were significantly (p < 0.05) more alpha2-ARs than alpha1-ARs in the myometrium. As far as alpha2-ARs are concerned, LA alpha2-ARs were significantly (p<0.05) higher than HA alpha2-ARs in all tested tissues. Competition studies suggested that the rank order of potency of antagonists for alpha1-ARs was prazosin > phentolamine > yohimbine, whereas for alpha2-ARs the order of potency was yohimbine > or = phentolamine>prazosin. Functional assays performed on myometrium showed that noradrenaline, phenylephrine and clonidine elicited concentration-dependent contractions only in dioestrus and pro-oestrus preparations and that clonidine was more effective than phenylephrine as a contractile agent. It appeared that there were no significant modifications in alpha-AR affinity or concentration during the different stages of bovine oestrous cycle, whereas the uterine spontaneous activity and the responsiveness to alpha-adrenergic stimulation was strongly influenced by hormonal levels. The modifications of uterine contractility observed during the oestrous cycle may be related to modifications induced in the transductional mechanisms of alpha-ARs.
Adrenergic alpha-Antagonists↗
Characterization of alpha-adrenoceptor subtypes in smooth muscle of equine ileum.
OBJECTIVE: To determine the concentration and binding characteristics of alpha-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 alpha-adrenoceptor subtypes was assessed by use of radioligand binding assays incorporating [3H]-prazosin and [3H]-rauwolscine, highly selective alpha1- and alpha2-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 alpha1- and alpha2-adrenoceptors were detected. Concentration of low-affinity alpha2-adrenoceptors was significantly greater in male horses, compared with females. Competition studies confirmed the specificity of the radioligands used in the binding assays. Alpha1-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 alpha2-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 alpha1- and alpha2-adrenoceptors were detected in smooth muscle of equine ileum. Because alpha-adrenoceptor subtypes, particularly alpha2-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.
Adrenergic alpha-Antagonists↗
Modifications of receptor concentrations for adrenaline, steroid hormones, prostaglandin F2alpha and gonadotropins in hypophysis and ovary of dairy cows with ovarian cysts.
Receptor concentrations for adrenaline, steroid hormones, PGF2alpha, LH and FSH were measured in the hypophysis and ovary of dairy cows with ovarian cysts and the results were compared with those of healthy animals. Significant modifications were found in all receptor concentrations, either between follicular and luteal structures or between the hypophyseal and ovarian receptorial status. The correlations between catecholaminergic and steroidal systems have already been demonstrated, particularly those existing between beta-adrenoceptors and steroid hormone receptors. Particular attention has been given to the possibility that a derangement in neurogenic inputs may be at the basis of some ovarian pathologies. The results of the present study suggest that the modifications of the ovarian and hypophyseal receptorial status of healthy and affected cows could play an important role in the pathogenesis of ovarian cysts.
Animals↗
Canine dilated cardiomyopathy: lymphocyte and cardiac alpha(1)- and beta-adrenoceptor concentrations in normal and affected great danes.
Serum catecholamine levels and myocardial and lymphocyte adrenergic receptor (AR) concentrations were measured in adult great danes affected by canine dilated cardiomyopathy (DCM) and compared to those of healthy animals. A non-homogeneous population of beta -AR, consisting of beta(1)-AR and beta(2)-AR, was observed in healthy (41 and 59%, respectively) and affected (17 and 83%, respectively) dog lymphocytes. Binding assays revealed that total beta -AR, beta(1)-AR and alpha(1)-AR were significantly downregulated (P<0.05;P<0.01;P<0. 001), both in lymphocyte and myocardial cell membranes of affected dogs. beta(2)-Adrenergic receptor concentrations were significantly reduced only in lymphocyte and right atrium cell membranes (P<0.05). Downregulation was not associated with alterations in receptor binding characteristics, as no significant differences in K(d)values were found. Mean plasma catecholamine levels were significantly higher (P<0.01) in DCM dogs (939+/-41) than in normal subjects (348+/-32), thus suggesting a sympathetic activation. The present study indicates a condition similar to that observed in human patients affected by DCM and that adrenergic receptors in canine lymphocytes reflect the fluctuation of adrenergic receptor concentrations in the myocardium.
Adrenergic alpha-Antagonists↗
Enhanced responsiveness of blood pressure to sodium intake and to angiotensin II is associated with insulin resistance in IDDM patients with microalbuminuria.
We assessed blood pressure (BP), body weight, renal hemodynamics, and insulin sensitivity (by euglycemic-hyperinsulinemic clamp) in nine normoalbuminuric and seven microalbuminuric IDDM patients after 6 days on a low-sodium diet (20 mEq) and after 6 days on a high-sodium diet (250 mEq). In microalbuminuric but not in normoalbuminuric IDDM patients, switching from a low to a high-sodium diet was associated with a significant increase in mean BP (from 92 +/- 3 to 101 +/- 4 mmHg; P < 0.001) and in body weight (2.91 +/- 0.63 vs. 1.47 +/- 0.26 kg; P < 0.05). Moreover, under high-sodium conditions, angiotensin II infusion (3 ng x kg(-1) x min(-1)) caused a greater increase in mean BP (14 +/- 2 vs. 7.4 +/- 1 mmHg; P < 0.05) and a smaller reduction in renal plasma flow (-122 +/- 29 vs. -274 +/- 41 ml x min(-1) x 1.73 m2; P < 0.05) in microalbuminuric than in normoalbuminuric IDDM patients. Under low sodium conditions, aldosterone increments after angiotensin II infusion were lower (P < 0.05) in microalbuminuric than in normoalbuminuric IDDM patients. Insulin-mediated glucose disposal was not affected by sodium dietary content, but it was lower in microalbuminuric (P < 0.05) than in normoalbuminuric IDDM patients. The salt-induced changes in mean BP were related to insulin sensitivity (r = -0.78; P < 0.001). In conclusion, in IDDM patients, microalbuminuria is associated with 1) an increased responsiveness of BP to salt intake and angiotensin II, 2) impaired modulation of renal blood flow, and 3) insulin resistance. Therefore, salt sensitivity in IDDM patients clusters with other factors that are likely to play an important role in the pathogenesis of diabetic nephropathy and its cardiovascular complications.
Adrenal Glands↗
Identification of beta-adrenergic receptor subtypes mediating relaxation in isolated equine ileum.
OBJECTIVE: To identify beta-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 beta-atypical and beta 2-adrenergic receptors. Binding studies on cell membranes indicated that the total beta-adrenergic receptors population consists of 54% beta-atypical, 34% beta 2- and 12% beta 1-subtypes. CONCLUSIONS: The data suggest that sympathetic relaxation of equine ileum smooth muscle depends mainly on beta-atypical receptor subtypes activation, with a minor contribution by beta 2-subtypes. CLINICAL RELEVANCE: The important role of beta-atypical adrenergic receptor subtypes in the relaxation of equine ileum suggests possible clinical use of selective beta-atypical receptor agonists to control intestinal disturbances.
Adrenergic beta-Agonists↗
Differences between longitudinal and circular smooth muscle in beta-adrenergic control of motility of isolated equine ileum.
OBJECTIVE: To identify beta-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 beta-adrenergic agonists exerted inhibitory effects on circular muscle preparations. Binding studies of cell membranes indicated that the density and distribution of 3 beta-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 beta-stimulation confirmed presence of the 3 adenylate cyclase-coupled beta-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 beta-atypical adrenoceptors in the inhibitory regulation of equine ileum motility.
Adrenergic Agonists↗
Down-regulation of beta-adrenergic receptors and up-regulation of estrogen and progesterone receptors induced in the reproductive system of female veal calves by dietary clenbuterol.
Effects induced by long-term administration of clenbuterol at anabolic dosages (20 micrograms/kg of body weight for 40 days) on beta-adrenergic receptor (beta-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 beta-AR subtypes (beta 1-AR, beta 2-AR, myometrial high-affinity beta 2-AR, and ovarian low-affinity beta 2-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 beta-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 beta-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 beta-adrenergic stimulation.
Adrenergic beta-Agonists↗
Specific binding of dl-cloprostenol and d-cloprostenol to PGF2 alpha receptors in bovine corpus luteum and myometrial cell membranes.
Prostaglandin F2 alpha receptors (PGF2 alpha Rs) were measured in bovine corpus luteum and myometrial cell membranes using a radiometric method. The inhibition of labelled PGF2 alpha binding exerted by d-cloprostenol, dl-cloprostenol, PGF2 alpha and PGE1 (10(-11) M to 10(-4) M) was evaluated in vitro. Results strongly suggest that cloprostenol binding to PGF2 alpha Rs is stereospecific. d-Cloprostenol and PGF2 alpha were equipotent, about 150 times more potent than dl-cloprostenol (P < 0.05) and approximately 280 times more potent than PGE1 (P < 0.05) in inhibiting [3H]PGF2 alpha binding to corpus luteum cell membranes. Such differences were less evident in myometrial cell membranes, where d-cloprostenol and PGF2 alpha were about 10 times more potent than dl-cloprostenol (P < 0.05) and approximately 95 times more potent than PGE1 (P < 0.05).
Animals↗
Regulation of uterine estrogen receptors (ER) by beta-adrenergic stimulation in immature rats.
The effects of a 3-day intramuscular (i.m.) administration of clenbuterol (25 micrograms/Kg), propranolol (12 mg/kg), clenbuterol (25 micrograms/kg) plus propranolol (12 mg/Kg) and estradiol (0.5 microgram) upon the female reproductive system were investigated in immature Sprague-Dawley rats. Clenbuterol and estradiol treatments induced a significant increase in uterus weight and in relative uterus weight, whereas in the groups treated with propranolol and clenbuterol plus propranolol no differences were detected versus controls. The uterine estrogen receptor levels were significantly increased by clenbuterol administration. In the rats dosed with propranolol and clenbuterol plus propranolol, no modifications occurred in estrogen receptor concentrations when compared with control values. Uterine progesterone receptors were never significantly affected by any of the considered treatments. Data obtained indicate that clenbuterol treatment induces an increase in uterus weight and in estrogen receptor levels and that these effects are regulated by acute beta-adrenergic stimulation, as the contemporaneous administration of high doses of a beta-blocker inhibit such effects.
Animals↗
Effects of long-term administration of clenbuterol in mature female rats.
Female Sprague-Dawley rats were treated IM with 0, 2.5, 25, and 50 micrograms 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.
7-Alkoxycoumarin O-Dealkylase↗
Effects of a beta 2-agonist (clenbuterol) on cultured human (CG-5) breast cancer cells.
In order to gain further knowledge about the possible oestrogen-like activities of clenbuterol (a beta 2-adrenergic drug illegally used as partitioning agent in food producing animals), we treated a hormone dependent human breast cancer cell line (CG-5) with different concentrations of the drug (10(-3) M to 10(-8) M). The effects of clenbuterol and oestradiol on cell proliferation were compared. Both oestradiol and clenbuterol, at low concentrations (10(-7) M and 10(-8) M) stimulated cell proliferation, but the effects of clenbuterol were less marked and significant. Probably clenbuterol elicited cell proliferation through a different mechanism, since it did not affect the cellular oestrogen receptor concentration. Clenbuterol failed in binding to the high affinity oestrogen receptors present in the CG-5 cells. As the beta-adrenergic receptors and the susceptibility to their stimulation have been recently demonstrated in vivo and in vitro in many tumour and normal cells, it is reasonable to suppose that clenbuterol may induce cell proliferation through beta-adrenergic stimulation.
Breast Neoplasms↗
Mediastinal chondrosarcoma. Case report.
A 34-year-old man and a 71-year-old woman underwent radical removal of mediastinally sited chondrosarcoma, presumably originating in the periosteum of the vertebral body. The man (with mesenchymal chondrosarcoma) died of remote metastasis 6 years postoperatively. The woman (poorly differentiated chondrosarcoma, grade 2-3) is still alive 2 years after the operation.
Adult↗
Evidence for functional beta-adrenoceptor subtypes in CG-5 breast cancer cell.
beta-adrenergic receptors (beta-ARs) were identified in CG-5 breast cancer cells using a radiometric assay. The total beta-AR concentration was measured using the highly potent beta-adrenergic antagonist (-)[3H]CGP 12177, and the densities of beta-AR subtypes were discriminated in the presence of highly selective unlabelled ligands (CGP 20712A and ICI 118551). Scatchard analysis revealed good linearity (r > 0.95) and Kd values (0.05-1 nM) indicated the presence of high affinity binding sites in CG-5 cell membranes. beta 2-AR concentrations (74%) were significantly (P < 0.05) higher than beta 1-AR concentrations (36%). Displacement studies indicated that tested adrenergic agonists displaced (-) [3H]CGP 12177 from its specific binding sites in the order of potency (-)isoproterenol > (+/-)clenbuterol > (-)adrenaline > (+/-)dobutamine > > (-)noradrenaline, whereas beta-adrenergic antagonists inhibited the binding in the following order of potency: (-)propranolol > > ICI 118 551 > > CGP 20712A. The functionality of beta-ARs identified in CG-5 cell membranes was demonstrated by the significant increase in cAMP production induced by different concentrations of isoproterenol vs unstimulated cells (control). The pathophysiological role of beta-ARs in breast cancer cells is still undefined, but their presence suggests the possible adrenergic regulation of some cellular activities such as proliferation and/or differentiation.
Breast Neoplasms↗
Blood kinetics of sulfamonomethoxine and oxytetracycline following intrauterine spray injection in dairy cows.
Intrauterine administration was performed in six Friesan cows with a disposable spray preparation containing 3 g of sulfamonomethoxine and 3 g of oxytetracycline, in order to investigate their serum kinetics. Sulfamonomethoxine levels were determined by a reversed-phase HPLC method, whilst oxytetracycline quantities were detected by a microbiological method. The sulphonamide had a peak 1.17 h after the administration, the tetracycline reached its highest concentration after 8 h. The bioavailability of both drugs was low and detectable drug amounts were no longer recovered after 24 h.
Animals↗
Identification of beta-adrenoceptor subtypes in bovine ovarian and myometrial cell membranes.
Beta-adrenoceptor (beta-AR) concentrations were measured in the ovary and in the myometrium of 36 adult Friesian cows using a radiometric assay. The beta-AR content in both tissues was determined using the highly specific antagonist (-) [3H]CGP 12177 and the amounts of beta-AR subtypes were discriminated in the presence of highly selective unlabelled ligands (CGP 20712A, ICI 118 551, CGP 25827A). Scatchard analysis revealed a good linearity and Kd values suggested the existence of high affinity beta-adrenergic sites in the bovine genital tract. Total beta-AR concentrations in the ovary and in the myometrium were, respectively, 87 +/- 7 (SEM) and 240 +/- 27 fmol mg-1 of membrane protein. beta 2-AR concentrations were significantly higher (P < 0.01) in the ovary (66 +/- 5) and the myometrium (180 +/- 29) than those of beta 1-AR (21 +/- 4 and 60 +/- 5, respectively). Significant differences (P < 0.05) were also to be found between high affinity state beta 2-AR and low affinity beta 2-AR concentrations, but their values correlated negatively in the two different tissues. Natural and synthetic agonists inhibited (-) [3H]CGP 12177 binding to beta-AR in the following order of potency: (-)isoproterenol > (+/-)clenbuterol > or = (-)adrenaline >> >> (-)noradrenaline, whereas synthetic antagonists inhibited binding in the following order of potency: (-)propranolol >> (+/-)ICI 118 551 >> >> (+/-)CGP 20712A.
Animals↗
Distribution of cytoplasmic estrogen (ER) and progesterone (PgR) receptors in bovine genital tract.
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Animals↗