The role of norepinephrine and nitric oxide in activities of rat arginine vasopressin neurons in response to immune challenge.

To explore the potential role of norepinephrine (NE) and nitric oxide (NO) in activities of rat hypothalamus arginine vasopressin (AVP) neurons in response to immune challenge, we observed the effect of prazosin, an antagonist of alpha1-adrenergic receptor, and the specific nitric oxide synthase (NOS) inhibitor N(w)nitro-L-arginine-methylester (L-NAME) on the Fos expression in AVP neurons induced by systemic lipopolysaccharide (LPS) using double immunohistochemistry. Intravenous (i.v.) injection of LPS induced Fos expression in AVP neurons mainly in the hypothalamus paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). The percentage of Fos-positive AVP neurons was dose-dependent. Pretreatment with prazosin (5 mg/kg) effectively suppressed the Fos expression induced by LPS (5 microg/kg), whereas L-NAME (30 mg/kg) did not influence the Fos expression in the AVP neurons induced by LPS (0.25, 0.5, 1, 5 microg/kg). Our results suggest that the activation of central AVP neurons caused by systemic LPS may be mediated by NE through alpha1-adrenergic receptors, but could not be changed by NO.

Effect of clonidine on colonic motility in rats.

Clonidine, an alpha(2)-adrenoceptor agonist, has been reported to inhibit gastric and small intestinal motility in rats. Whether clonidine also inhibits colonic motility is still not clear. The aim of this study was to examine the effect of clonidine on colonic motility and its possible site of action in adult Wistar rats. Colonic motilities in anesthetized rats in vivo or motilities of the isolated colon of rats in vitro were recorded. Clonidine was administered intravenously (i.v.) and intracerebroventricularly (i.c.v.) in vivo while bath administration was used in in vitro study. Clonidine i.v. or i.c.v. significantly inhibited colonic motility. This inhibitory effect was antagonized by pre-administration of yohimbine, an alpha(2)-adrenoceptor antagonist, but not by pre-administration of prazosin, an alpha(1)-adrenoceptor antagonist. Also, we have unpublished data indicating that the sympathectomy antagonized the inhibitory effect of systemically administered clonidine. A significant depression of colonic motility on the isolated colon was induced by bath administration of noradrenaline, while no such inhibition was seen by clonidine. The results of the present study suggested that clonidine inhibits colonic motility in rats through activation of central alpha(2)-adrenergic receptor.

Effect of indomethacin on the c-fos expression in AVP and TH neurons in rat brain induced by lipopolysaccharide.

The aim of the present study was to investigate the effect of indomethacin on the Fos expression in arginine vasopressin (AVP)-containing neurons in the hypothalamus and tyrosine hydroxylase (TH)-containing neurons in the locus coeruleus (LC) using dual-labeled immunohistochemistry. In the hypothalamus, intraperitoneal (i.p) injection of different doses [2.5 microg/100 g, 125 microg/100 g body weight (b.w.)] of lipopolysaccharide (LPS) induced a significant Fos expression in AVP neurons in the supraoptic nucleus (SON), the magnocellular division (mPVN) and the parvocellular division (pPVN) of the paraventricular nucleus (PVN). Pretreatment with the cyclooxygenase inhibitor indomethacin (0.8 mg/100 g b.w.) significantly blocked the Fos expression in these AVP neurons induced by a low dose of LPS (2.5 microg/100 g) but had no effect on the Fos expression induced by a high dose of LPS (125 microg/100 g). Similarly, in the brain stem, a large number of TH-positive neurons in the LC expressed Fos after administration of either dose of LPS. Indomethacin prevented the Fos expression induced only by a low dose of LPS, but not by a high dose of LPS. These results suggest that the activation of AVP neurons in PVN and SON and TH neurons in LC response to immune challenge might be mediated-at least partially-by prostaglandins.

The sympathetic nervous system is involved in the inhibitory effect of morphine on the colon motility in rats.

The role of the sympathetic nervous system in the inhibitory effect of morphine on colonic motility was investigated in male adult Wistar rats. The responses of colonic motility and blood pressure to the intravenous administration of morphine under urethane anesthesia were recorded. Sympathectomy (6-hydroxydopamine) or pretreatment with phentolamine, an alpha-adrenoreceptor antagonist (3.15 microM/kg, i.v.), or propranolol, a beta-adrenoreceptor antagonist (3.38 microM/kg, i.v.), on the inhibitory effect of intravenously administered morphine on colonic motility were observed. The results of the investigation showed that a significant depression of colonic motility occurred in untreated rats following intravenous administration of morphine, while no significant effect was seen in the sympathectomized. Pretreatment with phentolamine or propranolol also significantly attenuated the depression of colonic motility induced by morphine. Morphine also produced a transient depression of the blood pressure. However, this inhibitory effect of morphine on blood pressure was intensified after sympathectomy or pretreatment with either phentolamine or propranolol. We conclude that sympathetic activity plays an important role in the inhibitory effects of morphine on colonic motility and that both alpha- and beta-adrenoreceptors are involved.