Adrenoceptors in avian and fish pigment cells

Very little is known about the neurohumoral control of avian pigmentation and about adrenergic subtypes mediating catecholaminergic-controlled color change in nonmelanophore pigment cells of poikilothermic vertebrates. To determine the adrenoceptor subtypes in avian melanocytes and fish GEM-81 competitive binding assays were performed with the following radioactive ligands and their cold ligand counterparts: [3H]prazosin and benoxathian or unlabeled prazosin; [3H]rauwolscine and idazoxan or yohimbine; [3H]propranolol and metoprolol or ICI 118,551 and [125I]iodocyanopindolol and ICI 118,551. Our results suggest that: alpha(1)-adrenoceptors [K(i)=1.38 micro M; maximum displacement (md)=80%, benoxathian), alpha(2)-adrenoceptors (K(i)=0.21 micro M; md=82%, idazoxan), and beta(2)-adrenoceptors (K(i)=7.3 micro M; md=73%, ICI 118,551) are expressed in avian melanocytes, and that alpha(2)-adrenoceptors (K(i)=1.24 nM, idazoxan, K(i)=59 nM, yohimbine, md=65%, idazoxan and yohimbine; K(i)=0.19 nM, md=69%, prazosin), beta(1)-adrenoceptors (K(i)=22.2 micro M, md=75%, metoprolol), and beta(2)-adrenoceptors (K(i)=32.2 micro M, md=92%, ICI 118,551) are expressed in GEM-81 erythrophoroma cells. This may be the first study to show the presence of adrenoceptors in avian melanocytes and one of a few characterizing adrenoceptor subtypes in teleost nonmelanophore pigment cells.     

Alpha-2 adrenergic and opioid receptor-mediated gastroprotection.

Clonidine inhibited the development of gastric mucosal lesions induced by either acidified ethanol or indomethacin. The ED50 values were: 7.1 and 5.2 microg x kg(-1) orally, respectively. The gastroprotective effect was antagonised by the pre-synaptic alpha-2 antagonist yohimbine, the more selective alpha-2 antagonist Ch-38083 and the pre-synaptic alpha-2B antagonist prazosin. Moreover, the non-selective opioid receptor antagonist naloxone, the delta receptor selective naltrindole also reversed the clonidine-induced mucosal protective action. Clonidine was also effective following intracerebroventricular administration with the ED50 of 37 ng/rat against ethanol-induced mucosal damage. Our results suggest that: 1) the gastroprotective effect of clonidine is likely to be mediated by alpha-2B adrenoceptor subtype; 2) there is an interaction between pre-synaptic alpha-2 adrenoceptors and opioid system; and 3) clonidine can induce gastroprotection by central mechanism.     

Effects of cocaine alone and in combination with haloperidol and SCH 23390 on cardiovascular function in squirrel monkeys

The potential involvement of D1 and D2 dopamine receptors in the effects of cocaine on cardiovascular function in squirrel monkeys was evaluated. A low dose of cocaine (0.1 mg/kg i.v.) produced increases in both blood pressure and heart rate. At the higher doses of cocaine (1.0-3.0 mg/kg) the heart rate response was biphasic, consisting of an early decrease followed by an increase in heart rate 10-20 min following injection. The dopamine D2 antagonist haloperidol (0.1 mg/kg i.m.) attenuated the heart rate increasing effect of cocaine, but doses as high as 0.03 mg/kg did not alter the blood pressure increase. The D1 antagonist SCH 23390 (0.01-0.03 mg/kg i.m.) did not attenuate either the blood pressure or heart rate increasing effects of cocaine. The D2 agonist quinpirole (1.0 mg/kg i.v.) produced increases in heart rate similar to cocaine, with little effect on blood pressure. Although effective against the heart rate increasing effect of cocaine, haloperidol (0.01 mg/kg) did not antagonize the heart rate increasing effects of quinpirole. The D1 agonist SKF 38393 (3.0 mg/kg i.v.) decreased heart rate and increased blood pressure. The blood pressure increasing effect of SKF 38393 was antagonized by 0.01 mg/kg SCH 23390. Haloperidol's ability to partially antagonize the tachycardiac response to cocaine suggests the involvement of D2 receptors in that response. However, the failure of haloperidol to antagonize quinpirole's tachycardiac effect suggests that non-dopaminergic mechanisms may also be involved in haloperidol's antagonism of cocaine's tachycardiac effect. The pressor effects of cocaine do not appear to be controlled by selective dopamine receptors.     

Analysis of responses to sympathetic nerve stimulation in the feline pulmonary vascular bed

The adrenergic receptor subtypes mediating the response to sympathetic nerve stimulation in the pulmonary vascular bed of the cat were investigated under conditions of controlled blood flow and constant left atrial pressure. The increase in lobar vascular resistance in response to sympathetic nerve stimulation was reduced by prazosin and to a lesser extent by yohimbine, the respective alpha 1- and alpha 2-adrenoceptor antagonists. Moreover, in animals pretreated with a beta-adrenoceptor antagonist to prevent an interaction between alpha- and beta 2-adrenoceptors, responses to nerve stimulation were reduced by prazosin, but yohimbine had no significant effect. On the other hand, in animals pretreated with a beta-adrenoceptor antagonist, yohimbine had an inhibitory effect on responses to tyramine and to norepinephrine. Propranolol had no significant effect on the response to nerve stimulation, whereas ICI 118551, a selective beta 2-adrenoceptor antagonist, enhanced responses to nerve stimulation and injected norepinephrine. The present data suggest that neuronally released norepinephrine increases pulmonary vascular resistance in the cat by acting mainly on alpha 1-adrenoceptors and to a lesser extent on postjunctional alpha 2-adrenoceptors but that this effect is counteracted by an action on presynaptic alpha 2-receptors. The present studies also suggest that neuronally released norepinephrine acts on beta 2-adrenoceptors and that the response to sympathetic nerve stimulation represents the net effect of the adrenergic transmitter on alpha 1-, alpha 2-, and beta 2-adrenoceptors in the pulmonary vascular bed.     

Biphasic effects of yohimbine on the ejaculatory response in the dog

The effects of various doses (0.01-1.00 mg/kg) of yohimbine, an alpha-2 adrenoceptor antagonist, on the erectile and ejaculatory response elicited by manual penile stimulation were investigated in male dogs. Systemic administration of yohimbine caused a biphasic effect on ejaculatory response; the amount of ejaculate produced by the genital stimulation (for 5 min) was dose-dependently increased by low doses (0.01-0.10 mg/kg) of yohimbine, whereas it was decreased by the highest dose (1.00 mg/kg) of yohimbine. The erectile potency was attenuated only, by the highest dose of yohimbine. The most effective dose (0.10 mg/kg) of yohimbine on ejaculation did not affect the duration of penile erection after removing the genital stimulation. In a stereoisomer's testing, the stimulatory effect on ejaculation was also observed by rauwolscine, an alpha-2 adrenoceptor antagonist (0.03 and 0.10 mg/kg), but not by corynanthine, an alpha-1 adrenoceptor antagonist (0.10 and 0.30 mg/kg). These results suggest that yohimbine at low doses specifically facilitate the ejaculatory response through the blockade of the alpha-2 adrenoceptors. This study also indicates that the effects of yohimbine on male genital responses vary with its dosage used.     

Central adrenoceptors and basal prolactin release in the rat

The influence of the central adrenergic system on basal prolactin secretion was investigated in the rat. Several selective adrenoceptor blockers were centrally administered and their effects on prolactin secretion were observed. Blockade of beta-1 receptors by practolol, beta-2 receptors by IPS 339 and alpha-2 receptors by DG-5128 did not modify basal prolactin secretion, but alpha-1 adrenoceptor blockade by prazosin strongly enhanced prolactin plasma levels. These findings suggest that noradrenergic pathways in the central nervous system exert inhibitory tone on basal prolactin secretion, and that this effect seems to be mediated by alpha-1 adrenoceptors.     

Alpha-adrenergic stimulation of phosphatidylinositol synthesis in human platelets as an alpha-2 effect secondary to platelet aggregation

Epinephrine and adenosine diphosphate (ADP) stimulated 3H-glycerol uptake into phosphatidylinositol of human platelets. Yohimbine, an alpha-2 adrenoceptor antagonist, markedly reduced epinephrine-stimulated 3H-glycerol uptake into phosphatidylinositol; while prazosin, an alpha-1 antagonist, was without effect. Likewise, yohimbine, but not prazosin, blocked epinephrine-induced platelet aggregation. Furthermore, clonidine, a specific agonist for alpha-2 adrenoceptors, stimulated incorporation of 3H-glycerol into phosphatidylinositol and promoted platelet aggregation in the presence of low concentrations of ADP. These studies indicate that the effects of epinephrine on platelet aggregation and phosphatidylinositol synthesis are mediated through alpha-2 adrenoceptors. Further, since the stimulation of phosphatidylinositol synthesis seen with epinephrine was also observed with ADP, this suggests that the increased 3H-glycerol labeling is an indirect result of platelet aggregation.     

Hypothalamic alpha-adrenergic blockade modifies drinking and blood pressure responses to central angiotensin II in conscious rats

These experiments investigated in the awake rat the involvement of noradrenergic projections to the rostral hypothalamus in the drinking and pressor responses elicited by intracerebroventricular (i.c.v.) injections of 25 ng of angiotensin II. Phentolamine mesylate in doses of 2.5-125 micrograms injected into the rostral hypothalamus produced a dose-dependent depression of both the drinking and pressor responses elicited by i.c.v. administration of angiotensin II. A paradoxical increase in heart rate was associated with a decrease in pressor responses with increasing doses of phentolamine. This response was due to tissue injections, since pretreatment by injecting 12.5 micrograms of phentolamine into the ventricle did not block either the cardiovascular or drinking responses to i.c.v. injections of angiotensin II. Yohimbine (0.33-3.3 micrograms), DL-propranolol (25 micrograms), and atenolol (25 micrograms) did not, but prazosin (0.7 microgram) did significantly alter the pressor responses. Although yohimbine also was without effect on drinking, prazosin reduced the drinking responses. These results suggest that alpha 1-adrenergic receptors in the rostral hypothalamus are involved in the control of both the drinking and pressor responses elicited by i.c.v. injections of angiotensin II. In the case of propranolol and atenolol, beta-adrenergic receptors altered only the drinking response in a nonspecific manner by eliciting competing behaviors. Whether they are involved in modifying the drinking response only remains to be demonstrated.     

Noradrenergic stimulation of BDNF synthesis in astrocytes: mediation via alpha1- and beta1/beta2-adrenergic receptors

Brain-derived neurotrophic factor (BDNF) synthesis in astrocytes induced by noradrenaline (NA) is a receptor-mediated process utilizing two parallel adrenergic pathways: beta1/beta2-adrenergic/cAMP and the novel alpha1-adrenergic/PKC pathway. BDNF is produced by astrocytes, in addition to neurons, and the noradrenergic system plays a role in controlling BDNF synthesis. Since astrocytes express various subtypes of alpha- and beta-adrenergic receptors that have the potential to be activated by synaptically released NA, we focused our present study on the mediatory role of adrenergic receptors in the noradrenergic up-regulation of BDNF synthesis in cultured neonatal rat cortical astrocytes. NA (1 microM) elevates BDNF levels by four-fold after 6 h of incubation. Its stimulation was partly inhibited by either the beta1-adrenergic antagonist atenolol, the beta2-adrenergic antagonist ICI 118,551, or by the alpha1-adrenergic antagonist prazosin, while the alpha2-adrenergic antagonist yohimbine showed no effect. BDNF levels in astrocytes were increased by the specific beta1-adrenergic agonist dobutamine and the beta2-adrenergic agonist salbutamol, as well as by adenylate cyclase activation (by forskolin) and PKA activation (by dBcAMP). However, none of the tested agonists or mediators of the intracellular beta-adrenergic pathways were able to reach the level of NA's stimulatory effect. BDNF cellular levels were also elevated by the alpha1-adrenergic agonist methoxamine, but not by the alpha2-adrenergic agonist clonidine. The increase in intracellular Ca2+ by ionophore A23187 showed no effect, whereas PKC activation by phorbol 12-myristate 13-acetate (TPA) potently stimulated BDNF levels in the cells. The methoxamine-stimulated BDNF synthesis was inhibited by desensitizing pretreatment with TPA, indicating that the alpha1-stimulation was mediated via PKC activation. In conclusion, the synthesis of astrocytic BDNF stimulated by noradrenergic neuronal activity is an adaptable process using multiple types (alpha1 and beta1/beta2) of adrenergic receptor activation.     

Effect of prazosin and yohimbine on systolic blood pressure and on renal norepinephrine content in DOCA-salt rats

We studied the effect of alpha-1 and alpha-2 blockers (prazosin and yohimbine) on systolic blood pressure (SBP) and on renal norepinephrine (NE) content in Sprague-Dawley normotensive and DOCA-salt rats. The administration of desoxycorticosterone acetate (DOCA) to these rats for 6 weeks increased their SBP from 137 to 183 mmHg (p less than .001). This increase was prevented by simultaneous administration of prazosin (p less than .001), yohimbine (p less than .01), or prazosin + yohimbine (p less than .001). DOCA rats on saline and on yohimbine had lower renal NE content (p less than .05 and p less than .001, respectively) than normotensive rats. Renal NE content of DOCA rats on yohimbine decreased with respect to those treated with prazosin (p less than .001) or prazosin + yohimbine (p less than .05). Besides, renal NE content of DOCA rats on prazosin increased when compared to control DOCA rats (p less than .05). However, these drugs showed no effect on SBP and on renal NE content in normotensive rats. These findings further confirm that the alpha adrenoceptor blockade can prevent the hypertension of DOCA-salt rats in such a way that their blood pressure stabilizes at similar levels to those observed in normotensive treated animals.     

Interaction Between Nociceptin/Orphanin FQ and Adrenergic System on Food Intake in Neonatal Chicken

The information emerging from the studies demonstrates adrenergic system and nociceptin/orphanin FQ (N/OFQ) play a crucial role on appetite regulation but there is no information for their interaction. The purpose of this study was to examine the effects of intracerebroventricular (ICV) injection of prazosin (α₁ receptor antagonist), yohimbine (α₂ receptor antagonist), metoprolol (β₁ adrenergic receptor antagonist), ICI 118,551 (β₂ adrenergic receptor antagonist) and SR59230R (β₃ adrenergic receptor antagonist) on N/OFQ-induced hyperphagia by 3-h food-deprived neonatal broiler chicken. In experiment 1, chicken injected with saline, prazosin (10 nmol), N/OFQ (16 nmol) and co-injection of prazosin + N/OFQ. In experiment 2, ICV injection of saline, yohimbine (13 nmol), N/OFQ (16 nmol) and yohimbine + N/OFQ applied to the birds. In experiment 3, injections were saline, metoprolol (24 nmol), N/OFQ (16 nmol) and metoprolol + N/OFQ. In experiment 4, the birds received ICV injection of saline, ICI 118,551 (5 nmol), (C) N/OFQ (16 nmol) and co-administration of ICI 118,551 + N/OFQ. In experiment 5, chicken injected with saline, SR59230R (20 nmol), N/OFQ (16 nmol) and SR59230R + N/OFQ. Then, cumulative food intake was recorded until 120 min after injection. According to the results, ICV injection of N/OFQ significantly increased food intake (P < 0.001). The effect of N/OFQ significantly amplified by co-injection of N/OFQ + β₂ adrenergic receptor antagonist (P < 0.001). Also, administration of β₁ or β₃ adrenergic receptor antagonist had no effect on N/OFQ-induced hyperphagia (P > 0.05). These results suggest that the effect of N/OFQ on cumulative food intake is mediated via β₂ adrenergic receptors in neonatal chicken.     

Effect of beta-antagonists on isoprenaline-induced secretion of fluid, amylase and protein by the parotid gland of the red kangaroo, Macropus rufus

Selective and non-selective beta-adrenoceptor antagonists were used to block the increases in fluid, protein and amylase secretion caused by sympathomimetic stimulation of the parotid gland of red kangaroos during intracarotid infusion of isoprenaline. ICI118551 at antagonist/agonist ratios up to 300:1 caused increasing but incomplete blockade of fluid secretion, and protein/amylase release. Atenolol at antagonist/agonist ratios up to 300:1 was only marginally more potent than ICI118551 at blocking the fluid, protein and amylase responses. Propranolol at antagonist/agonist ratios of 30:1 was as effective at blocking fluid and protein secretion as the highest ratios of either atenolol or ICI118551. Simultaneous administration of atenolol (30:1) with ICI118551 (30:1) was not as potent as propranolol (30:1). Thus, the beta-adrenoceptor/s in the acini of the kangaroo parotid gland appear to have antagonist-binding affinities atypical of those found for eutherian tissues. The data are consistent with the gland possessing either a single anomalous beta-adrenoceptor or functional beta(2)-receptors in addition to the beta(1)-receptors which are characteristic of eutherian salivary glands.     

Uterine motility in the cow during the estrous cycle. III. Effects of oxytocin, xylazine, and adrenoceptor blockers

Intrauterine pressure (IUP) was recorded in nonlactating dairy cows using an intraluminal catheter with two micropressure transducers located 15 cm apart at the distal end. There was a significant increase (P < 0.05) in IUP following administration of xylazine and oxytocin at all four stages of the estrous cycle. The most significant increase in IUP occurred during proestrus for both drugs. The effect of pretreatment with adrenoceptor-blocking agents on IUP changes induced by xylazine and oxytoxin was evaluated. Alpha-1 adrenoceptor blockade (prazosin) had no effect on IUP following xylazine treatment. However, alpha-2 adrenoceptor blockade (yohimbine) resulted in a reduction (P < 0.05) in IUP compared to controls. Neither prazosin or yohimbine affected oxytocin-induced IUP.     

Characterization of postjunctional adrenoceptor subtypes in isolated rat myocardial cells in culture

The effects of agonists and antagonists, specific for the different adrenoceptor subtypes on the automaticity of cultured ventricular cells from postnatal rat, were studied. Chronotropic responses were assessed by recording monophasic action potentials using intracellular microelectrodes. Contraction was assessed by an electro-optical procedure. (-)-Isoproterenol, salbutamol, (-)-phenylephrine, and methoxamine increased the spontaneous rate in a dose-dependent manner, but the stimulatory potencies of alpha-adrenoceptor agonists were weaker than those of the beta-alternates. The frequency response to (-)-isoproterenol was inhibited by atenolol but not by butoxamine. Atenolol was also more effective than butoxamine in antagonizing the rate acceleration by salbutamol. The chronotropic effects of phenylephrine and methoxamine were inhibited by prazosin. In contrast, neither clonidine nor yohimbine displayed any chronotropic action. These findings suggest that the postjunctional adrenoceptors present in the sarcolemma of the isolated cardiac muscle cells, which mediate automaticity responses to catecholamines, are of beta 1, beta 2, and alpha 1 types, the physiological contribution of the beta 1-adrenoceptors being predominant. Applicability of these conclusions to the in situ myocardiocytes is discussed with respect to the level of functional differentiation achieved by the rat myocardial cells in culture.     

Role of adrenoceptors and cAMP on the catecholamine-induced inhibition of proteolysis in rat skeletal muscle

The role of adrenoceptor subtypes and of cAMP on rat skeletal muscle proteolysis was investigated using a preparation that maintains tissue glycogen stores and metabolic activity for several hours. In both soleus and extensor digitorum longus (EDL) muscles, proteolysis decreased by 15-20% in the presence of equimolar concentrations of epinephrine, isoproterenol, a nonselective beta-agonist, or clenbuterol, a selective beta(2)-agonist. Norepinephrine also reduced proteolysis but less markedly than epinephrine. No change in proteolysis was observed when muscles were incubated with phenylephrine, a nonselective alpha-agonist. The decrease in the rate of protein degradation induced by 10(-4) M epinephrine was prevented by 10(-5) M propranolol, a nonselective beta-antagonist, and by 10(-5) M ICI 118.551, a selective beta(2)-antagonist. The antiproteolytic effect of epinephrine was not inhibited by prazosin or yohimbine (selective alpha(1)-and alpha(2)-antagonists, respectively) or by atenolol, a selective beta(1)-antagonist. Dibutyryl cAMP and isobutylmethylxanthine reduced proteolysis in both soleus and EDL muscles. The data suggest that catecholamines exert an inhibitory control of skeletal muscle proteolysis, probably mediated by beta(2)-adrenoceptors, with the participation of a cAMP-dependent pathway.     

Effect of catecholamine on aldosterone release in isolated rat glomerulosa cell suspensions

Effect of adrenergic activity on the adrenal steroidogenesis and the modulation by catecholamines of aldosterone release were studied in isolated rat adrenal cell suspensions. Isoproterenol, norepinephrine and epinephrine, but not dopamine, caused statistically significant increase in aldosterone release. Both prazosin (alpha 1 antagonist) and yohimbine (alpha 2 antagonist) suppressed the norepinephrine-induced aldosterone release in a dose dependent manner, respectively. Both atenolol (beta 1 antagonist) and ICI 118-551 (beta 2 antagonist) also blocked (-)-isoproterenol-induced aldosterone release in a dose dependent manner, respectively. Neither (-)-isoproterenol nor (+/-)-norepinephrine at concentrations of 10(-6) M potentiated aldosterone release stimulated by angiotensin II or ACTH. These results suggest that catecholamines stimulate aldosteroidogenesis, but it appears unlikely that aldosterone release induced by ACTH or angiotensin-II is modulated by adrenergic stimulation.     

Involvement of the opioid system in the central antisecretory action of alpha-2 adrenoceptor agonists in rat

The aim of the present study was to analyse the role of the central alpha-2 adrenoceptors in the regulation of gastric acid secretion in pylorus ligated rats. It was found that the intracerebroventricularly (icv.) injected presynaptic alpha-2 adrenoceptor agonist clonidine and the alpha-2A adrenoceptor subtype selective stimulant oxymetazoline exerted a dose dependent inhibition on gastric acid secretion. The antisecretory ED(50) values for clonidine and oxymetazoline were 20 and 7.5 nmol/rat icv., respectively. The antisecretory effect of these compounds was antagonised by the presynaptic adrenoceptor antagonist yohimbine (50 nmol/rat icv.) indicating that the action is mediated through central presynaptic alpha-2 adrenoceptors. Moreover, naloxone (50 nmol/rat icv.)--non-selective opioid antagonist--and naltrindole (0.5 nmol/rat icv.)--delta-opioid receptor selective antagonist--also decreased the antisecretory effect of clonidine and oxymetazoline suggesting that the endogenous opioid system is likely to be involved in the central antisecretory action of alpha-2 adrenoceptor stimulants.     

Effect of adrenoblockers on the analgesic effect of GABA-positive preparations

The experiments on rats have shown that selective alpha 1 and alpha 2 adrenoceptor blockers (prazosin and yohimbine) and an inhibitor of dopamine-beta-hydrolase FD-008 failed to change the antinociceptive effect of baclofen, a direct GABAB receptor agonist. The antinociceptive effect of THIP and depakin, acting predominantly on GABAA receptors, was significantly reduced by prazosin, FD-008 and yohimbine in vocalization test. In tail-flick test the analgetic effect of THIP and depakin was not altered by prazosin and FD-008, but was increased by yohimbine. The role of adrenergic mechanisms in GABAA and GABAB receptor-mediated analgesia is discussed.     

Norepinephrine Induces Apoptosis in Skin Melanophores by Attenuating cAMP‐PKA Signals Via α2‐Adrenoceptors in the Medaka,Oryzias Latipes

The density of skin melanophores in many teleost fish decreases during long‐term adaptation to a white background. Using the medaka, Oryzias latipes, we previously reported that apoptosis is responsible for the decrease in melanophores, and that a sympathetic neurotransmitter, norepinephrine (NE), induces their apoptosis in skin tissue cultures. In this study, we show that NE‐induced apoptosis of melanophores is mediated by the activation of α2‐adrenoceptors. Clonidine, an α2‐adrenoceptor agonist, induced apoptotic melanophore death in skin organ culture, while phenylephrine, an α1‐adrenoceptor agonist, had no effect. NE‐induced apoptosis was diminished by an α2‐adrenoceptor antagonist, yohimbine, but an α1‐adrenoceptor antagonist, prazosin, did not abrogate the effect of NE. Furthermore, forskolin inhibited NE‐induced apoptosis, while an inhibitor of PKA, H‐89, mimicked the effect of NE. These results suggest that NE induces apoptosis in melanophores by attenuating cAMP‐PKA signaling via α2‐adrenoceptors.     

Effect of Chronic Restraint Stress on Human Colorectal Carcinoma Growth in Mice

Stress alters immunological and neuroendocrinological functions. An increasing number of studies indicate that chronic stress can accelerate tumor growth, but its role in colorectal carcinoma (CRC) progression is not well understood. The aim of this study is to investigate the effects of chronic restraint stress (CRS) on CRC cell growth in nude mice and the possible underlying mechanisms. In this study, we showed that CRS increased the levels of plasma catecholamines including epinephrine (E) and norepinephrine (NE), and stimulated the growth of CRC cell-derived tumors in vivo. Treatment with the adrenoceptor (AR) antagonists phentolamine (PHE, α-AR antagonist) and propranolol (PRO, β-AR antagonist) significantly inhibited the CRS-enhanced CRC cell growth in nude mice. In addition, the stress hormones E and NE remarkably enhanced CRC cell proliferation and viability in culture, as well as tumor growth in vivo. These effects were antagonized by the AR antagonists PHE and PRO, indicating that the stress hormone-induced CRC cell proliferation is AR dependent. We also observed that the β-AR antagonists atenolol (ATE, β1- AR antagonist) and ICI 118,551 (ICI, β2- AR antagonist) inhibited tumor cell proliferation and decreased the stress hormone-induced phosphorylation of extracellular signal-regulated kinases-1/2 (ERK1/2) in vitro and in vivo. The ERK1/2 inhibitor U0126 also blocked the function of the stress hormone, suggesting the involvement of ERK1/2 in the tumor-promoting effect of CRS. We conclude that CRS promotes CRC xenograft tumor growth in nude mice by stimulating CRC cell proliferation through the AR signaling-dependent activation of ERK1/2.