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Nitric oxide and prostaglandins in the clenbuterol-induced ACTH and corticosterone secretion

100%

Gadek-Michalska A., Bugajski A. J., Bugajski J.

Journal of Physiology and Pharmacology

2008

tom 59

nr 1

The present study was designed to determine the involvement of nitric oxide (NO) and prostaglandins (PG) in the stimulatory action of clenbuterol, a selective ß2-adrenergic receptor agonist on hypothalamic-pituitary-adrenal (HPA) axis under basal and social crowding stress conditions. Clenbuterol given i.c.v. (10 µg) or i.p. (0.2 mg/kg) considerably increased ACTH and corticosterone secretion. A selective ß2-receptor antagonist compound ICI 118551 and non-selective ß-receptor antagonist propranolol given by either route reduced the stimulatory action of clenbuterol. Crowding stress (21 rats in a cage for 7) for 3-7 days significantly reduced the i.c.v. clenbuterol-induced ACTH and corticosterone secretion and i.p. clenbuterol-elicited ACTH secretion. L-NAME, mainly endothelial nitric oxide synthase (NOS) blocker, stronger than L-NNA, a neuronal NOS blocker, reduced the clenbuterol-evoked ACTH and corticosterone secretion in control rats but did not significantly alter this secretion already reduced by crowding stress. Piroxicam, predominantly constitutive cyclooxygenase (COX-1) inhibitor, given i.p. significantly diminished the i.p. clenbuterol-induced ACTH and corticosterone secretion in control rats and tended to reverse the reduction of ACTH secretion by crowding stress. These results indicate that clenbuterol, a selective ß2-adrenoceptor agonist, is much stronger stimulator of the HPA axis than isoprenaline, a non-selective ß-receptor agonist. Social crowding stress reduces to a larger extent the HPA response to ß2-receptor stimulation. Likewise, in the HPA axis stimulation via ß2-adrenoceptors endogenous NO and prostaglandins are significantly involved. Beta2-adrenoceptor is a dominant functional subtype of ß-receptor in the stimulatory and modulatory signals regulating the HPA axis activity under basal and social stress conditions.

Indirect role of beta2-adrenergic receptors in the mechanism of anti-inflammatory action of NSAIDs

59%

Suleyman H., Halici Z., Cadirci E., Hacimuftuoglu A., Bilen H.

Journal of Physiology and Pharmacology

2008

tom 59

nr 4

661-672

In this study we investigated both intact and adrenalectomized rats to determine whether or not the anti-inflammatory effects of indomethacin, diclofenac sodium, ibuprofen, nimesulide, tenoxicam and aspirin (IDINTA) are related to adrenal gland hormones in carrageenan-induced inflammation model of rats. Also, we investigated the anti-inflammatory action mechanism of hormones (adrenalin, cortisol) which perform a role in the anti-inflammatory effect of IDINTA on the adrenergic receptors. The results show that IDINTA produces significant anti-inflammatory effects in intact rats (ID50: 9.82, 10.81, 95.21, 75.23, 8.21 and 61.84 mg/kg), but insignificant effects in adrenalectomized rats (ID50: 152.97, 188.17, 1275.0, 433.67, 188.16 and 1028.17 mg/kg). In addition, adrenalin and prednisolone caused anti-inflammatory effect rates of 78.3% and 95.7% respectively in adrenalectomized rats. The anti-inflammatory effects of adrenalin and prednisolone did not change when prazosin (1-receptor blocker), yohimbine (2-receptor blocker) and phenoxybenzamine (1- and 2- receptor blocker) were given to rat groups; however, in adrenalectomized rats administered with propranolol (a non-selective blocker of ß1 and ß2-receptors) the anti-inflammatory effect of adrenalin was lost, and that of prednisolone decreased to 36.2%. It was also found that metoprolol (a selective blocker of ß1-receptors) did not alter the anti-inflammatory effects of the drugs. As a result, it was shown that anti-inflammatory effects of IDINTA are related to adrenalin and cortisol (corticosterone in rats). It was also determined for the first time that adrenalin (totally) and prednisolone (partially) triggered anti-inflammatory effects via the ß2-receptors but not via the 1, 2 and ß1-receptors.

Ograniczanie wyników

2 Journal of Physiology and Pharmacology

1 Bilen H.

1 Bugajski A. J.

1 Bugajski J.

1 Cadirci E.

1 Gadek-Michalska A.

1 Hacimuftuoglu A.

1 Halici Z.

1 Suleyman H.

2 2008

Wyniki wyszukiwania

Nitric oxide and prostaglandins in the clenbuterol-induced ACTH and corticosterone secretion

Indirect role of beta2-adrenergic receptors in the mechanism of anti-inflammatory action of NSAIDs