Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now generally accepted, that in most of the animal species the adrenergic control of lipolysis from adipose tissue is mediated by adrenergic beta 1 and alpha 2 receptors. Therefore, the problem we deal with in this article is concerned with the role of alpha adrenergic receptors in lipolysis in the rat adipose tissue because only in this species the function of alpha adrenergic receptors in lipolysis is still not clear. In in vitro experiments with epididymal adipose tissue of adult rats (where we followed up the release of free fatty acids into the albumin medium) we found: 1) Alpha adrenergic blocking agents phentolamine and phenoxybenzamine had no influence on the lipid mobilizing effect of adrenergic agonists. This effect was absent also when drugs with the strong alpha sympathomimetic effects, e.g. norepinephrine and noroxedrine, were used. 2) On the other hand, alpha adrenergic agonist phenylephrine was able to antagonize in rat adipose tissue the lipid mobilizing effect of beta adrenergic agonist isoproterenol. 3) From our experiments it can be concluded, that phenylephrine acts as a competitive dualist on beta adrenergic receptors, it reduces the effect of full agonist (e.g. isoproterenol) to the level of its own maximum lipolytic effect. No participation of alpha adrenergic receptors in described effects of phenylephrine were detected, because neither the lipolytic, nor the lipolysis blocking effects of phenylephrine were influenced by alpha adrenergic blocking agents. Our studies using alpha adrenergic agonist phenylephrine or nonselective alpha adrenergic blocking agents did not indicate the presence of any alpha adrenergically controlled lipolysis in the rat adipose tissue. However, the role of antilipolytic alpha 2 adrenoceptors in rat adipose tissue cannot be completely excluded, some of these receptors were found on the membranes of rat adipocytes. Our future study deals with this problem.
 ...
PMID:[The effect of alpha adrenergic agents on lipolysis in rat adipose tissue; the effect of nonselective alpha adrenomimetics and alpha adrenolytics in an experiment in vitro]. 168 69

1 The effects of some sympathomimetic amines and of carbachol and potassium chloride upon the contractility of epididymal halves of the rat vas deferens have been examined in vitro at several times following vasectomy by medial transection of the vas deferens in vivo. The inhibitory effects of noradrenaline and the excitatory effects of potassium chloride upon prostatic halves of transected tissues were also studied. 2 Partially denervated epididymal segments, taken 2 days after surgery, were spontaneously active, and responses to KCl (80 mmol/l) and maximum responses to phenylephrine were enhanced. These effects were not observed with preparations taken at later times. Spontaneous activity and enhancement of responses to KCl were abolished by guanethidine (0.1 mumol/l). 3 Supersensitivity to noradrenaline was observed in fully denervated epididymal halves of vasa deferentia taken 7-183 days after transection. The supersensitivity consisted of a leftward shift in the log concentration-response curves for noradrenaline constructed upon operated, relative to those obtained upon unoperated preparations. Supersensitivity to phenylephrine but not to methoxamine or to carbachol was also evident. 4 The magnitude of the leftward shift in the log concentration-response curve for noradrenaline in operated epididymal segments approached that produced, in unoperated segments, by nisoxetine (0.1 mumol/l). This inhibitor of neuronal uptake did not enhance the potency of noradrenaline in operated segments. 5 Prazosin (50 nmol/l) antagonized the effect of phenylephrine upon both operated and unoperated epididymal segments. The antagonism was significantly greater upon operated segments than upon unoperated segments 4 and 28 days after surgery. 6 In prostatic segments, noradrenaline produced inhibition of field stimulation-induced twitches. Its potency was similar in both operated and unoperated preparations, and nisoxetine (0.1 mumol/l) potentiated its effects to a similar extent (approximately 70-fold) in control and operated tissues. Responses to KCl in this half of the vas deferens were essentially unaffected by vasectomy. 7 Taken together, these findings indicate that post-ganglionic denervation of the epididymal half of the rat vas deferens by medial transection (vasectomy) leads to a slowly developing and prolonged supersensitivity to noradrenaline which is primarily due to the loss of the neuronal uptake facility. Persistent adaptive changes in the effector cells are apparently minimal after this means of denervation.
 ...
PMID:Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy. 289 40

In this paper, estimates of the selectivities of a series of twelve sympathomimetic agents acting at postjunctional alpha 1- and prejunctional alpha 2-adrenoreceptors were investigated, using epididymal and prostatic segments of the rat vas deferens. The relative order of potency for the twelve agonists at prejunctional alpha 2-adrenoreceptors mediating inhibition of field-stimulation-induced contractions in the prostatic segment of the vas deferens was: clonidine greater than (-)-adrenaline greater than xylazine greater than or equal to (-)-noradrenaline greater than (+)-adrenaline greater than dopamine greater than or equal to phenylephrine greater than or equal to metaraminol greater than or equal to (+)-noradrenaline greater than (-)-isoprenaline greater than methoxamine greater than (+)-isoprenaline. The relative order of potency for the agonists at postjunctional alpha 1-adrenoreceptors mediating contraction of smooth muscle in epididymal segments of the vas deferens was: (-)-adrenaline greater than or equal to (-)-noradrenaline greater than phenylephrine greater than clonidine greater than or equal to (+)-adrenaline greater than or equal to methoxamine greater than or equal to (+)-noradrenaline greater than or equal to metaraminol greater than or equal to dopamine greater than or equal to (-)-isoprenaline greater than or equal to xylazine; (+)-isoprenaline was inactive. (+)-Noradrenaline, the stereoisomers of adrenaline and isoprenaline, dopamine, clonidine, xylazine and metaraminol displayed alpha 2-selectivity whereas phenylephrine and methoxamine displayed alpha 1-adrenoreceptor selectivity. (-)-Noradrenaline possessed a similar potency at both alpha 1- and alpha 2-adrenoreceptors thus making it non-selective by the criteria used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Selectivities of some agonists acting at alpha 1- and alpha 2-adrenoreceptors in the rat vas deferens. 300 22

Insertion of Silastic rods containing the directly acting sympathomimetic drug, methoxamine, adjacent to the epididymis of rats caused a temporary reduction in fertility with no loss of ability to mate. This effect lasted up to 3 weeks. At the time of the maximal antifertility action (3-7 days after insertion), the number of spermatozoa in the ejaculate fell to almost zero, and there was a reduction in the total number of spermatozoa in the epididymis resulting from a significant drop in the number present in the cauda. Methoxamine also caused immotility and decapitation of the remaining epididymal spermatozoa. The indirectly acting sympathomimetics, tyramine and norephedrine, did not affect fertility. It is postulated that methoxamine acts to induce infertility principally by bringing about a reduction of sperm numbers in the ejaculate. This could have been produced either by a failure of the vas and cauda to contract normally at copulation or because the sperm store in the cauda had fallen below a critical threshold level.
 ...
PMID:Effect of local application of sympathomimetic drugs to the epididymis on fertility in rats. 735 77

The present study was performed to determine the usefulness of the alpha-sympathomimetic midodrin for diagnosis and treatment of functional sperm transport disturbances. 140 andrological patients consulting due to severe oligozoospermia, hypospermia or partial/complete retrograde ejaculation were included. Ejaculates were examined 30 min after intravenous injection of 5-15 mg midodrin. Sperm concentration, motility and alpha-glucosidase as a marker of both epididymal function and sufficient passage through the vasa deferentia and the ejaculatory duct were measured and the values compared to those in the ejaculates obtained before therapy. In 23 of 140 patients, sperm concentration or total sperm count was improved by more than 10 million spermatozoa ml-1 or 20 million spermatozoa per ejaculation. Alpha-glucosidase in the seminal plasma increased in two cases. The present study demonstrates that severe oligozoospermia may be caused by functional transport disturbance of semen from the epididymis to the efferent duct system. In these cases, midodrin is of diagnostic and therapeutic value; however, it should be emphasized that its effectiveness cannot be predicted individually.
 ...
PMID:The alpha-sympathomimetic midodrin as a tool for diagnosis and treatment of sperm transport disturbances. 752 69

1. Carteolol, a non-selective beta-blocker with intrinsic sympathomimetic activity, admixed in a pellet diet was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin-dependent diabetes mellitus with mild obesity. A high dose of carteolol (0.02%) suppressed bodyweight gain without affecting food and water consumption until the appearance of glycosuria. Carteolol tended to reduce the cumulative incidence of glycosuria at 26 weeks after the beginning of administration (55, 17 and 25% in control rats, and in rats fed a low (0.002%) and high dose of carteolol, respectively). 2. At the 26th week of administration, the high dose of carteolol decreased visceral fat weight, such as that of retroperitoneal and epididymal adipose tissue, whereas the liver and the kidney were not affected. 3. Although plasma glucose and triglyceride levels in non-fasted rats were elevated with age, carteolol tended to delay the increases in those parameters. Carteolol suppressed the increase in plasma glucose levels, which indicate the diabetic pattern, in a 25th week oral glucose tolerance test. 4. These findings indicate that carteolol induces improvements in bodyweight and carbohydrate and lipid metabolism in an obese condition. Consequently, carteolol may be useful for the treatment of hypertension with obesity in order to prevent cardiovascular events.
 ...
PMID:Improving effect of carteolol on bodyweight and carbohydrate and lipid metabolic responses in the OLETF rat. 914 81

The only safe method of male contraception is vasectomy, with high reversibility secured by microsurgery. Italy, however, suffers from a lack of regulations on this subject. Hormonal treatment (testosterone plus progestational hormones) is far from providing reliability and safety, while some perspectives, theoretical only for the time being, are offered by studies on functional infertility induced by either speeding up (ganglioplegic, sympathomimetic, parasympatholytic, oxytocin, endothelin, angiotensin) or inhibiting (sympatholytic) the sperm transport through the epididymis, or altering the epididymal environment (alpha-chloridin, chlorodeoxyglucose).
 ...
PMID:[Male contraception]. 1553 63

The aim of the study was to investigate the effects of (1) macronutrients on food intake, body composition and serum resistin and adiponectin and (2) sibutramine(S) on the above parameters in rats fed with isocaloric diets. Three groups of male Wistar rats (n=63) were fed with high fat diet (HFD), high carbohydrate diet (HCD) or high protein diet (HPD) for 13weeks. In the last 3weeks each group was divided into three subgroups and received S 5mg/kg or 10mg/kg, or vehicle. Body weight was measured weekly, gastrocnemius muscle, perirenal, retroperitoneal and epididymal fat were isolated, fat/lean ratio was calculated and serum adiponectin and resistin were assayed. S did not affect lean body mass in any group. HFD was associated with elevated fat/lean ratio regardless of S administration. S at 10mg/Kg decreased fat/lean ratio in the HCD and HPD and adiponectin in the HFD group. S did not affect resistin in any group. Adiponectin was paradoxically elevated in the HFDS10 compared to the HCD or HPD S10 groups. Resistin was lower in the HCD compared to the HPD and HFD groups. Results suggest a preferential effect of S on body fat. The detrimental effect of S on adiponectin can be attributed to its sympathomimetic properties. Adiponectin was paradoxically elevated in the HFD and resistin in the HPD group, results that require further investigation.
 ...
PMID:Serum adiponectin and resistin in rats under three isocaloric diets: The effect of sibutramine. 1925 35

Sibutramine is a drug globally used for the treatment of obesity. The aim of this study was to investigate male reproductive disorders caused by sibutramine in adult rats. Wistar rats were treated for 28 consecutive days (gavage) with 10 mg/kg of sibutramine. Control animals received only vehicle (dimethylsulfoxide and saline). The rats were sacrificed for evaluation of body and reproductive organ weights, sperm parameters, hormone levels (luteinizing hormone, follicle-stimulating hormone, and testosterone), testicular and epididymal histopathology, sexual behavior, fertility and in vitro contractility of the epididymal duct. Sibutramine decreased (P < .05) weights of the epididymis and ventral prostate, but not of other reproductive organs. The sperm number and transit time in the epididymal cauda were decreased (P < .001), but the daily sperm production was not altered. Moreover, morphology and sperm motility, histopathology of the testes and epididymis, sexual behavior, fertility, and serum hormone levels were not altered by the treatment. Sibutramine increased the potency of norepinephrine and, per se, increased the mechanical activity of the epididymal duct in vitro. Thus, although sibutramine in these experimental conditions did not interfere with the reproductive process of rats, it provoked acceleration of the sperm transit time and a decrease in the sperm reserves in the epididymal cauda. This alteration is probably related to the sympathomimetic effect of this drug, as shown by the in vitro assays. In humans, use of this drug might present a threat for male fertility because sperm reserves in men are naturally lower than those in rats.
 ...
PMID:Acceleration of sperm transit time and reduction of sperm reserves in the epididymis of rats exposed to sibutramine. 2176 97

Sperm acquire motility and fertility capacity during epididymal transit, under the control of androgens and sympathetic innervations. It is already known that the acceleration of epididymal sperm transit time can lead to lower sperm quality. In a previous work we showed that rats exposed to the anorexigen sibutramine, a non-selective serotonin-norepinephrine reuptake inhibitor, presented faster sperm transit time, lower epididymal sperm reserves and potentiation of the tension of epididymal duct to norepinephrine exposed acutely in vitro to sibutramine. In the present work we aimed to further investigate pharmacological mechanisms involved in these alterations and the impact on rat sperm quality. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/day) or vehicle for 30 days. Sibutramine decreased final body, seminal vesicle, ventral prostate and epididymal weights, as well as sperm transit time in the epididymal cauda. On the contrary of the in vitro pharmacological assays, in which sibutramine was added directly to the bath containing strips of distal epididymal cauda, the ductal tension was not altered after in vivo sub-chronic exposure to sibutramine. However, there is pharmacological evidence that the endogenous epididymal norepinephrine reserves were reduced in these animals. It was also shown that the decrease in prostate weight can be related to increased tension developed of the gland, due to sibutramine sympathomimetic effects. In addition, our results showed reduced sperm quality after in utero artificial insemination, a more sensitive procedure to assess fertility in rodents. The epididymal norepinephrine depletion exerted by sibutramine, associated with decreases in sperm transit time, quantity and quality, leading to reduced fertility in this experimental model, reinforces the concerns about the possible impact on fertility of man taking sibutramine as well as other non-selective serotonin-norepinephrine reuptake inhibitors, especially considering the lower reproductive efficiency of humans compared to males of other species.
 ...
PMID:Slimmer or fertile? Pharmacological mechanisms involved in reduced sperm quality and fertility in rats exposed to the anorexigen sibutramine. 2377 14


1