The role of the hypothalamic beta-adrenergic system in controlling the LH rise in short-term castrated rats

Intraventricular infusions of adrenaline and various pharmacological agents acting on beta-adrenergic receptor subtypes were carried out in rats orchidectomized 16 h previously. Infusions (10 microliter) of solutions containing the drugs were administered under anaesthesia induced with alphaxalone and alphadolone. Levels of LH were measured in plasma collected immediately before and at predetermined intervals after the infusion. The acute rise in LH levels after castration was increased still further by isoprenaline (a mixed beta 1- and beta 2-agonist), fenoterol (a beta 2-agonist) and atenolol (a beta 1-antagonist). In contrast, prenalterol (a beta 1-agonist) and (2RS,3RS)-3-isopropylamino-1-(7-methylindan-4-yloxy)++ +butan-2-ol (ICI 118,551) (a selective beta 2-antagonist) were inhibitory to LH release. Adrenaline itself, salbutamol (another selective beta 2-agonist), propranolol (a mixed beta-antagonist) and metoprolol (a beta 1-antagonist) did not significantly alter plasma LH concentrations at the doses administered. The stimulatory effect of isoprenaline on LH release was partially reduced when given together with ICI 118,551, but was not affected when administered simultaneously with atenolol. The inhibitory effect of ICI 118,551 was, however, prevented by concomitant administration with fenoterol, as was that of prenalterol when infused with atenolol. The results suggest that the hypothalamic mediation of the short-term changes in LH release in response to castration is exerted, at least in part, through the activation of a beta 2-stimulatory component and the suppression of a beta 1-inhibitory component.     

Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men

OBJECTIVE: beta-Adrenoceptor-mediated whole-body lipolysis is impaired in obesity. This study investigated whether local adipocyte beta-adrenergic sensitivity and changes in nutritive blood flow in subcutaneous abdominal adipose tissue contribute to this impaired response. METHODS: Three microdialysis probes were placed in the subcutaneous abdominal adipose tissue of eight obese and nine lean men. Each probe was perfused with either 0.1, 1 and 10 microM isoprenaline; 1, 10 and 100 microM dobutamine or 1, 10 and 100 microM salbutamol, each dose for 45 min. RESULTS: At baseline, interstitial glycerol concentrations and ethanol out/in ratios were comparable between groups. During nonselective beta-, beta(1)- and beta(2)-adrenergic stimulation, interstitial glycerol concentrations increased and ethanol out/in ratios decreased similarly in obese and lean men. CONCLUSION: The lipolytic and nutritive blood flow response to beta(1)- beta(2)- and nonselective beta-adrenergic stimulation in situ is comparable in lean and obese male subjects. The present data suggest that a blunted beta-adrenergic sensitivity of the fat cell and an impaired local nutritive blood flow response do not contribute to the previously reported diminished whole-body beta-adrenoceptor-mediated lipolytic response in obese males.     

Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol)

Cardiovascular and peripheral adaptations to an aerobic conditioning program were studied in 30 hypertensive adults taking either placebo, beta 1-selective beta-adrenergic blocker (metoprolol) or beta 1-nonselective beta-adrenergic blocker (propranolol). The placebo group increased aerobic capacity (VO2max) 24% (p less than 0.002), largely explained by an increased peripheral arteriovenous (AV) oxygen difference with minimal changes in cardiac size and function. Resting blood pressure and total systemic resistance also decreased. The group taking a beta 1-selective beta blocker increased VO2max 8% (p less than 0.05), reduced resting blood pressure but had no significant change of AV oxygen difference or cardiac size or function. The group taking the beta 1-nonselective beta blocker propranolol had no increase in VO2max, no decrease in resting blood pressure and no cardiovascular or peripheral adaptations to the exercise program. Thus, beta 1-selective and beta 1-nonselective beta blockers attenuate conditioning in hypertensive patients to differing degrees, in each case by blocking peripheral mechanisms of conditioning.     

Coexistence of beta 1- and beta 2-adrenoceptors in human right atrium. Direct identification by (+/-)-[125I]iodocyanopindolol binding

The highly specific beta-adrenoceptor radioligand, (+/-)-[125I]iodocyanopindolol, has been used to subclassify beta-adrenoceptors in membranes from human right atrial appendage obtained during open heart surgery. Binding of (+/-)-[125I]iodocyanopindolol was saturable (Bmax = 86.4 +/- 7.4 fmol (+/-)-[125I]iodocyanopindolol bound/mg protein, n = 4), of high affinity (KD = 53 +/- 6 pM, n = 4), rapid, reversible, and stereospecific. The relative potencies of isoprenaline, adrenaline, and noradrenaline for inhibition of (+/-)-[125I]iodocyanopindolol binding and activation of adenylate cyclase were 1:10:10, indicating a population composed mainly of beta 1-adrenoceptors. Inhibition of (+/-)-[125I]iodocyanopindolol binding by beta 1- (practolol, metoprolol, betaxolol) and beta 2- (IPS 339, ICI 118,551, zinterol, procaterol) selective drugs, however, resulted in biphasic displacement curves with slope factors (nH, pseudo Hill coefficients) significantly less than 1.0. Nonlinear regression analysis of these curves revealed a beta 1: beta 2 ratio of 80:20 in human right atrial appendage. Nonselective beta-adrenergic drugs (propranolol, isoprenaline, and adrenaline), on the contrary, inhibited binding with monophasic displacement curves and nH = 1.0. Binding of agonists to the beta-adrenoceptors in human right atrial appendage seems to be regulated by guanyl nucleotides. In the absence of GTP, isoprenaline binds to high and low affinity state of the beta-adrenoceptors. GTP (10(-4) M) converts this heterogeneous binding into a homogeneous one of low affinity. It is concluded that, in human right atria, beta 1- and beta 2-adrenoceptors coexist; however, beta 1-adrenoceptors predominate. The physiological function of beta 2-adrenoceptors in human right atrium remains to be elucidated.     

The effect of non-selective and selective beta-1-blockade on the plasma potassium response to hypoglycaemia

The effect of non-selective beta-blockade with propranolol, beta 1-selective blockade with betaxolol and of saline on the plasma potassium response to insulin induced hypoglycaemia was examined in six healthy subjects. Although propranolol retarded the recovery from hypoglycaemia, the degree of hypokalaemia was significantly (p less than 0.01) less than with saline or betaxolol, which had similar effects. Adrenergic mechanisms may modulate potassium disposal through a beta 2 receptor.     

Beta-adrenergic control of motility in the rat colon. I. Evidence for functional separation of the beta 1- and beta 2-adrenoceptor-mediated inhibition of colon activity

The beta-adrenoceptor-mediated inhibitory response in isolated rat colon strips of beta-adrenoceptor agonists (isoproterenol, terbutaline, prenalterol) in the absence and presence of the selective beta-adrenoceptor antagonists metoprolol (beta 1) and IPS 339 (beta 2) demonstrates that both beta 1- and beta 2-adrenoceptors are involved in the inhibition of colonic motility. Neuronal blockade induced by tetrodotoxin suppressed the relatively high (68%) maximal response of prenalterol (partial beta-adrenoceptor agonist) to 23%. The concentration-response curves for terbutaline (beta 2-selective agonist) and isoproterenol (nonselective agonist) were not influenced by tetrodotoxin. The results thus indicate that the beta-adrenergic inhibition of spontaneous activity in the rat colon strip may be mediated at two functional levels within the colon wall: either by beta 2-adrenoceptors in the smooth muscle layer or by beta 1-adrenoceptors in the intramural ganglionic plexuses, which by neuronal elements are coupled to the effector smooth muscle.     

Catecholamine-sensitive adenylate cyclase of human fat cell ghosts: a comparative study using different beta-adrenergic agents.

Some of the effects of beta-adrenergic agonists and antagonists on the adenylate cyclase system of human fat cell ghosts were studied. Isoproterenol, by causing about a fourfold increase of enzyme activity, was more potent than epinephrine and norepinephrine (about 2.5--3.0-fold stimulation). The beta2-adrenergic agonists salbutamol, terbutalin, and fenoterol were considerably less effective than the naturally occurring catecholamines. The stimulatory actions of isoproterenol and beta2-adrenergic agonists were competitively inhibited by the beta-blocking agent propranolol. Isoproterenol stimulation was also inhibited by the selective beta1-adrenergic antagonist practolol. This compound, however, was less potent than propranolol. The results are suggestive for an adenylate cyclase system in human fat cell ghosts coupled to beta1-adrenergic receptor sites. These receptors differ from the cardiac beta receptors with respect to practolol affinity.     

Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors

OBJECTIVE: Circulating leptin, the product of the ob gene, is known to be closely correlated with adipose tissue mass, but it is also subject to short-term regulation by a variety of hormones including catecholamines. The aim of this study was to investigate the contribution of the three beta-adrenergic receptors to leptin secretion from cultured human adipocytes. DESIGN AND METHODS: The model of in vitro differentiated human subcutaneous adipocytes was used in this study. The presence of the beta-adrenoceptor subtypes was studied by RT-PCR. The functional role of the receptor subtypes was determined by stimulation of lipolysis by selective beta-adrenergic agonists and by measuring glycerol release. Leptin secretion into the medium of cultured human adipocytes from young normal-weight females was measured by radioimmunoassay. RESULTS AND CONCLUSION: In a first set of experiments, the expression of the three beta-adrenergic receptor subtypes in cultured human adipocytes was demonstrated. To test their functional activity, the effect of the beta-adrenoceptor agonists isoproterenol (non-selective agonist), dobutamine (beta(1)-selective), fenoterol (beta(2)-selective) and the beta(3)-selective agonists BRL 37344 and CGP 12177 was studied. All agonists exhibited a dose- and time-dependent stimulation of glycerol release into the medium in a rather uniform manner. Isoproterenol rapidly reduced leptin secretion from cultured subcutaneous adipocytes in a dose-dependent fashion. Incubation with 10(-6)mol/l isoproterenol for 24h resulted in a reduction of the leptin concentration by 48% (P < 0.01). A similar, but less pronounced suppressing effect was seen for dobutamine and fenoterol, whereas both BRL 37344 and CGP 12177 were not effective. These data provide evidence that catecholamines are able to suppress leptin release from differentiated human adipocytes, supporting the concept that leptin secretion is acutely regulated by surrounding hormones. This inhibition is obviously mediated via beta(1)- and beta(2)-adrenergic receptors.     

Intracoronary injections of salbutamol demonstrate the presence of functional beta 2-adrenoceptors in the human heart

To demonstrate the presence of functional cardiac beta 2-adrenoceptors in man, we studied the responses to intracoronary injections of salbutamol in three groups of six patients. We injected salbutamol, a selective beta 2-adrenoceptor agonist, into the right coronary artery to avoid peripheral vasodilator action and to stimulate the sinoatrial node directly. Salbutamol injections caused a sinus tachycardia. The same doses of salbutamol injected into the aortic root caused no change in heart rate, ruling out a systemic effect. The mean dose required to cause an increase in heart rate of 30 beats/min (IHR30) was 2.6 micrograms in the first group of six patients. In 12 other patients salbutamol was given after beta-blockade to confirm the beta 2-selectivity of the responses. Doses of practolol (beta 1-selective blockade) and of propranolol (beta 1- and beta 2-blockade) that had equal beta 1-blocking activity were used. In six patients who were given practolol, the mean IHR30 dose was 2.1 micrograms. In six patients who were given propranolol, the mean IHR30 dose was significantly greater at 64 micrograms (p less than 0.001, practolol vs. propranolol). This study demonstrates that direct cardiac beta 2-adrenoceptor stimulation in man has a positive chronotropic effect.     

Specific non-beta-adrenergic binding sites for 125I-iodocyanopindolol in myocardial membrane preparations: a comparative study between human, rat, and porcine hearts.

STUDY OBJECTIVE--The aim was to investigate observed differences in beta adrenergic and apparent non-beta-adrenergic binding of (-)[125I]-iodocyanopindolol (125I-ICYP). DESIGN--Binding parameters for several beta adrenergic agonists and antagonists were examined in radioligand binding assay, using 125I-ICYP as radioligand, in membranes prepared from myocardial tissue. SUBJECTS--Human right auricular myocardium was obtained from patients undergoing open heart surgery. Ventricular myocardium was from Norwegian landrace pigs and Wistar rats. MEASUREMENTS AND MAIN RESULTS--Specific binding of 125I-ICYP was observed. This was only partially competed for with high affinity by isoprenaline, noradrenaline, adrenaline, and atenolol. Considerable interspecies variations in the magnitude of specific non-beta-adrenergic (NBA) binding of 125I-ICYP were shown. The equilibrium constant of dissociation (Kd) of the specific NBA binding sites for 125I-ICYP was 0.3-0.4 nmol.litre-1, and the binding capacities were 20, 106, and 192 fmol.mg-1 protein in rat, human, and porcine myocardium, respectively. The NBA sites were heat sensitive and destroyed by trypsin. Association to NBA sites occurred more rapidly than to beta adrenoceptors. Dissociation of bound 125I-ICYP from NBA sites and beta adrenoceptors at 30 degrees C revealed first order kinetics with t1/2 of 19 min from NBA, as compared to 120 min from beta adrenoceptors. In all three species the ligand specificity for NBA sites was very similar and various adrenergic agonists and antagonists competed with 125I-ICYP binding with the following potencies: timolol greater than propranolol greater than ICI 118 551 greater than pindolol greater than Sandoz 204 545 greater than terbutaline greater than noradrenaline and adrenaline much greater than isoprenaline and atenolol. Of agonists and antagonists for other receptor systems, only the serotoninergic 5-HT2 antagonist ritanserin could displace 125I-ICYP from the NBA sites with relatively high affinity. CONCLUSIONS--125I-ICYP and several beta adrenoceptor antagonists interact specifically with receptor like proteins other than beta adrenoceptors, and remarkable interspecies difference in the levels of myocardial NBA sites was observed.     

Autoradiographic characterization of beta-adrenergic receptor subtype in the canine conduction system.

It has been hypothesized, based on physiological evidence, that there is a greater proportion of beta 2-adrenergic receptors on the myocytes of the conduction system when compared with the working myocardium. The purpose of these studies was to examine beta-adrenergic receptor subtype in the conduction system of the dog by using the technique of coverslip autoradiography. Scintillation studies of [125I]pindolol binding to ventricular sections demonstrated that binding was saturable (dissociation constant of 116 pM), had the correct order of potency for a beta-receptor, and was stereoselective. Both betaxolol (beta 1-selective) and ICI-118,551 (beta 2-selective) competition curves fit a two-site model in nonlinear curve-fitting analyses (78% beta 1-receptors). Autoradiographic studies determined that the myocytes of the sinoatrial node had approximately twice as many autoradiographic grains as the surrounding atrial myocytes. The myocytes of the atrioventricular bundle had a number of grains similar to the number in surrounding septal myocytes. Autoradiographic inhibition curves with betaxolol or ICI-118,551 demonstrated that both the sinoatrial node and the atrioventricular bundle had inhibition profiles similar to the surrounding myocytes (predominantly beta 1) but unlike the inhibition profiles of arterioles (predominantly beta 2). Calculations using the dissociation constants derived from the nonlinear curve-fitting analysis and the percent specific binding in the presence of 4 x 10(-7) M betaxolol or ICI-118,551 determined that the proportion of beta 1- to beta 2-receptors was the same (70-80% beta 1) when comparing the sinoatrial node and the surrounding atrial myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Effect of Adrenaline,Noradrenaline, Isoprenaline and Salbutamol on the Resting Levels of White Blood Cells in Man

Adrenaline, noradrenaline, isoprenaline and salbutamol were infused at the rate of 7 μg/min for 30 min into 5 healthy subjects. Pulse rates showed a marked increase after isoprenaline, a moderate increase after adrenaline and salbutamol, and a consistent decrease after noradrenaline. The total leucocyte counts increased in response to adrenaline and noradrenaline but remained unchanged after isoprenaline and salbutamol. The absolute lymphocyte counts showed significant increases after all the four agonists. Neutrophils increased in response to adrenaline and noradrenaline but remained unchanged after isoprenaline and salbutamol. ‘Stress’ lymphocyte counts rose in response to adrenaline, isoprenaline and salbutamol but not to noradrenaline. From these and other reported observations it is suggested that both α- and β- receptors are involved in the mobolization of lymphocytes, while neither has any specific role in the mobilization of neutrophils.     

The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle

beta-Adrenergic receptor (beta-AR) agonists induce Nur77 mRNA expression in the C2C12 skeletal muscle cell culture model and elicit skeletal muscle hypertrophy. We previously demonstrated that Nur77 (NR4A1) is involved in lipolysis and gene expression associated with the regulation of lipid homeostasis. Subsequently it was demonstrated by another group that beta-AR agonists and cold exposure-induced Nur77 expression in brown adipocytes and brown adipose tissue, respectively. Moreover, NOR-1 (NR4A3) was hyperinduced by cold exposure in the nur77(-/-) animal model. These studies underscored the importance of understanding the role of NOR-1 in skeletal muscle. In this context we observed 30-480 min of beta-AR agonist treatment significantly and transiently increased expression of the orphan nuclear receptor NOR-1 in both mouse skeletal muscle tissue (plantaris) and C2C12 skeletal muscle cells. Specific beta(2)- and beta(3)-AR agonists had similar effects as the pan-agonist and were blocked by the beta-AR antagonist propranolol. Moreover, in agreement with these observations, isoprenaline also significantly increased the activity of the NOR-1 promoter. Stable exogenous expression of a NOR-1 small interfering RNA (but not the negative control small interfering RNA) in skeletal muscle cells significantly repressed endogenous NOR-1 mRNA expression and led to changes in the expression of genes involved in the control of lipid use and muscle mass underscored by a dramatic increase in myostatin mRNA expression. Concordantly the myostatin promoter was repressed by NOR-1 expression. In conclusion, NOR-1 is highly responsive to beta-adrenergic signaling and regulates the expression of genes controlling fatty acid use and muscle mass.     

Binding of adrenergic ligands to liver plasma membrane preparations from the axolotl, Ambystoma mexicanum; the toad, Xenopus laevis; and the Australian lungfish, Neoceratodus forsteri

The beta-adrenergic ligand iodocyanopindolol (ICP) bound specifically to hepatic plasma membrane preparations from the axolotl, Ambystoma mexicanum (Bmax, 40 fmol/mg protein (P) at free concentration above 140 pM; KD, 42 pM); the toad, Xenopus laevis (Bmax, 200 fmol/mg P at 1 nM; KD, 300 pM); and the Australian lungfish, Neoceratodus forsteri (Bmax, 100 fmol/mg P at 5 nM). For the lungfish, the Scatchard plot was curved showing two classes of binding site with KD's of 20 and 500 pM. Neither the alpha 1-adrenergic ligand prazosin nor the alpha 2-adrenergic ligand yohimbine bound specifically to hepatic membrane preparations from any of the three species. Several adrenergic ligands displaced ICP from hepatic membrane preparations of all three species with KD's of Axolotl--propranolol, 50 nM; isoprenaline, 600 nM; adrenaline, 10 microM; phenylephrine, 20 microM; noradrenaline, 40 microM; and phentolamine, greater than 100 microM; X. laevis--propranolol, 30 nM; isoprenaline, 100 microM; adrenaline, 200 microM; noradrenaline, 300 microM; phenylephrine, 1 mM; and phentolamine, greater than 1 mM; N. forsteri,--propranolol, 25 nM; isoprenaline, 1 microM; adrenaline, 20 microM; phenylephrine, 35 microM; noradrenaline, 600 microM; and phentolamine, 400 microM. These findings suggest that alpha-adrenergic receptors are not present in hepatic plasma membrane preparations from these three species and that the hepatic actions of catecholamines are mediated via beta-adrenergic receptors. The order of binding of the beta-adrenergic ligands suggests that the receptors are of the beta 2 type.     

Abnormalities in the adrenergic control and the rate of lipolysis in isolated human subcutaneous adipose tissue in diabetes mellitus

Summary Subcutaneous adipose tissue was obtained from 9 patients with untreated diabetes mellitus and from 13 obese nondiabetics. After incubation with isoprenaline or noradrenaline, glycerol release and tissue cyclic AMP (cAMP) were determined. Basal glycerol release was twice as rapid from the diabetic adipose tissue. With isoprenaline, the cAMP concentration and the glycerol production was significantly higher in the diabetic adipose tissue. Noradrenaline did not increase glycerol production or cAMP concentration in the diabetic adipose tissue. Subcutaneous adipose tissue was also removed from the diabetics after antidiabetic treatment. Basal lipolysis was significantly reduced and noradrenaline significantly increased both glycerol release and cAMP production. With isoprenaline, cAMP productjon and glycerol release were significantly less after antidiabetic treatment than in the untreated state. The data provide evidence for increased - as well as -adrenergic receptor sensitivity in human subcutaneous adipose tissue of untreated diabetic patients.     

Aldosterone content of the blood and tissues in rats with an altered level of adrenergic activity

The content of aldosterone (A) was studied in rat adrenal glands, blood plasma and peripheral tissues--in the myocardium, skeletal muscles, thymus and liver--1 h after the administration of alpha-adrenergic stimulator noradrenaline and beta-adrenergic stimulator isoprenaline and after simultaneous administration of alpha- and beta-blockers and a sympatholytic agent (pyrroxan, propranolol and bretylium tosylate respectively). Adrenergic stimulation did not change the level of A in the adrenal glands, raised its blood concentration and, to a greater extent, its level in the peripheral tissues. A marked increase in the blood concentration of A resulted from isoprenaline and its accumulation in tissues--from noradrenaline. A decrease in the level of adrenergic activity considerably lowered the A content in the adrenal glands, blood plasma and peripheral tissues excluding the myocardium where this value was higher than in the blood.     

Subtypes of beta-adrenergic receptors in bovine coronary arteries

Whether large coronary artery dilation induced by beta-adrenergic stimulation is mediated by beta 1- or beta 2-adrenergic receptors remains controversial. This problem is particularly difficult to address in vivo due to the concomitant increase in coronary blood flow with beta-adrenergic stimulation, which by itself can dilate large coronary arteries. To reconcile this problem, 5 calves were instrumented with intraaortic and intracoronary (i.c.) catheters, ultrasonic diameter transducers, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. Two to six weeks following surgery, beta-adrenergic agonists were administered i.c. to avoid complicating systemic effects. Isoproterenol (0.0025 micrograms/kg, a beta 1 + beta 2-adrenergic agonist) increased coronary diameter (7.1 +/- 0.8% from 5.80 +/- 0.58 mm) (p less than 0.01). Similar increases (p less than 0.01) in coronary diameter occurred with prenalterol (0.4 micrograms/kg, beta 1-adrenergic agonist) (9.5 +/- 1.4%) and pirbuterol (0.25 micrograms/kg, beta 2-adrenergic agonist) (8.1 +/- 1.2%). When coronary blood flow was prevented from rising with the hydraulic constrictor, increases in coronary diameter to all three beta-adrenergic agonists were not attenuated. Large coronary artery dilation with prenalterol and pirbuterol was abolished with beta 1- and beta 2-adrenergic receptor blockade, respectively, while neither beta 1- nor beta 2-adrenergic blockade alone abolished the large coronary artery dilation with isoproterenol. To identify the predominant subtype of beta-adrenergic receptor, competitive inhibition curves utilizing 125I-cyanopindolol (125I-CYP) as the radiolabel versus isoproterenol, epinephrine, and norepinephrine were generated in membrane preparations from calf heart (predominant beta 1), calf lung (predominant beta 2) and calf coronary artery. The coronary artery membrane preparations demonstrated an intermediate pattern. Competition curves with selective beta 1- and beta 2-adrenergic receptor agonists and antagonists again demonstrated a pattern for coronary artery intermediate to that of heart and lung, further confirming the presence of both beta-adrenergic receptor subtypes in large coronary arteries, with a ratio of beta 1: beta 2 of 1.5-2.0:1.0. Thus, large coronary arteries of the calf contain both beta 1- and beta 2-adrenergic receptors identified utilizing ligand binding techniques, and stimulation of both receptor subtypes in the intact conscious animal results in large coronary artery dilation, independent of blood-flow-mediated vasodilation.     

Peripheral progesterone concentrations in the luteal-phase ewe: effects of a beta-adrenergic receptor antagonist and two beta 2-adrenergic agonists

Peripheral blood samples were collected at 10-min intervals from three conscious sheep in which ovulation had been induced 6-10 days previously using exogenous hormones. Saline was infused into a jugular vein for about 1 h, followed by the experimental drug for 1-2 h and followed by saline again for a further 2 h. The experiments were repeated following induced luteolysis and ovulation. The infusion of a beta-adrenergic antagonist (propranolol) into three conscious luteal-phase ewes decreased (P less than 0.05) the peripheral progesterone concentration in each animal. Infusions of beta 2-adrenergic agonists (ritodrine and salbutamol) increased (P less than 0.05) the progesterone concentration in four out of eight experiments. The beta-adrenergic antagonist decreased the heart rate and the beta 2-adrenergic agonist increased it; the arterial blood pressure and respiratory rate were unaffected. The decrease in the progesterone concentration in response to the beta-adrenergic antagonist suggests that the normal ovarian secretion of progesterone is partly the result of sympathetic stimulation, and that the sympathetic innervation of the ovary may have a physiological role in modulating progesterone secretion.     

Catecholamine stimulation of cortisol secretion by 3-day primary cultures of purified zona fasciculata/reticularis cells isolated from bovine adrenal cortex

Primary cultures of zona fasciculata/reticularis cells derived from bovine adrenal cortex secreted cortisol and corticosterone in response to isoprenaline, noradrenaline and adrenaline on the third day of culture. The potency order was isoprenaline greater than noradrenaline, adrenaline with an ED50 for all three agonists within the range 1-5 x 10(-8) M. A dose-dependent increase in medium content of cyclic AMP was also observed. Secretion of cortisol in response to these catecholamines was specifically blocked by propranolol but unaffected by phentolamine. The beta-agonist effect on cortisol secretion was specifically and progressively reduced, in a time- and dose-dependent manner, by pre-incubation of the cells with adrenaline.     

Catecholamine receptor sensitivity and the regulation of lipolysis in adult diabetes

Summary The sensitivity of alpha- and beta-adrenergic receptors, and the antilipolytic actions of prostaglandin E₁ or insulin on adipose tissue of obese diabetic and non-diabetic subjects have been studied. Accumulation of cyclic AMP in adipose tissue and release of glycerol in response to several catecholamines (adrenaline, noradrenaline and isoprenaline) in the presence or absence of an alpha-adrenergic blocker (phentolamine) have been used to assess catecholamine receptor sensitivity. No differences in beta-receptor activity were observed between diabetics and non-diabetics, either on glycerol release or accumulation of cyclic AMP; alpha-receptor activity was also similar, except for significantly less accumulation of cyclic AMP in diabetic tissue incubated with noradrenaline and phentolamine (p<0.01). The antilipolytic action of prostaglandin E₁ (at concentrations of 30 fM to 30 pM) on lipolysis (stimulated submaximally with isoprenaline, 10^–7 M) was similar in diabetic and control groups. The antilipolytic action of insulin (from 10^–10 to 10^–6 M) on lipolysis was also similar between the groups. It is concluded that neither disorders of the catecholamine receptor nor of the antilipolytic actions of prostaglandin E₁ or insulin are responsible for the abnormalities of fatty acid metabolism in adult diabetes.