The effects of selective manipulations of activity of the serotonergic and noradrenergic systems were examined in the rat model of visceral pain. It was found that neither p-chlorophenylalanine(p-CPA)- nor N-chloro-ethyl-2,2--bromo-benzylamine(DSP-4)-induced strong and selective depletion of the brain and spinal cord serotonin and noradrenaline, respectively, changed in a significant way rat vi...

Noradrenaline, like most other neurotransmitters, acts through various adrenoceptor subtypes. The structure and active site of adrenoceptors for the binding of noradrenaline were unknown, however, such information are crucial for understanding the molecular mechanism of action of neurotransmitters, including noradrenaline, in health and disease as well as for drug designing. In this in silico s...

(R)-6-[(3-{[4-(5-{[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}pent-1-yn-1-yl)phenyl] carbamoyl}phenyl)sulphonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide trifluoroacetic acid (GS-5759) is a bifunctional ligand composed of a quinolinone-containing pharmacophore [β2-adrenoceptor agonist orthostere (β2A)] found in several β2-adrenoceptor agonists, including...

BACKGROUND During androgen ablation prostate cancer cells' growth and survival become independent of normal regulatory mechanisms. These androgen-independent cells acquire the remarkable ability to adapt to the surrounding microenvironment whose factors, such as neurotransmitters, influence their survival. Although findings are becoming evident about the expression of alpha(1A)-adrenoceptors in...

Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV) reduced cold allodynia in sciatic nerve chronic constriction injury (CCI) rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg) was performed into Zusanli acupoint 2...

In patients with high thoracic spinal lesions that remove most of the central drive to splanchnic preganglionic neurons, visceral or nociceptive stimuli below the lesion can provoke large increases in blood pressure (autonomic dysreflexia). We have examined the effects of T4 spinal transection on isometric contractions of mesenteric arteries isolated from spinalized rats. Nerve-evoked contracti...

Pharmacological differences between canine and monkey basilar arteries were studied in vitro. The constrictor response of canine basilar artery to either norepinephrine or an alpha 1-adrenoceptor agonist phenylephrine was partly inhibited by an alpha 2-adrenoceptor antagonist yohimbine but not by an alpha 1-adrenoceptor antagonist prazosin. The contraction elicited by an alpha 2-adrenoceptor ag...

OBJECTIVE Our investigation was designed to examine the signaling pathway involved in the enhancement of vascular endothelial growth factor (VEGF) release by β-adrenoceptor agonists. MATERIALS AND METHODS Human U937 cells differentiated into macrophages were primed with lipopolysaccharide (LPS) in the absence or presence of β-adrenoceptor agonists and antagonists. The VEGF released and the in...

The relation between insulin resistance/ hyperinsulinemia and cardiovascular disease may be related to one of the cardiovascular effects of insulin. In acute experiments in humans, systemic euglycemic hyperinsulinemia induced vasodilation in skeletal muscle. Furthermore, the sympathetic nervous system is activated, although this does not lead to increase in blood pressure (BP). We hypothesized ...

We have compared the vasopressor response of alpha-adrenoceptor agonists in young (2 month-old) and older (12 month-old) pithed rats both in the presence and absence of triiodo-L-thyronine (T3)-induced hyperthyroidism. There was no age-related changes in the pressor response to either the alpha 1-selective agonist phenylephrine or the alpha 2-selective agonists clonidine and UK-14,304. However,...