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Antagonist Prazosin (antagonist + prazosin)
Kinds of Antagonist Prazosin Selected AbstractsInteraction Between Norepinephrine, Oxytocin, and Nitric Oxide in the Stimulation of Gonadotropin-Releasing Hormone Release From Proestrous Rat Basal Hypothalamus ExplantsJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2004D. J. Selvage Abstract In the proestrous female rat, norepinephrine, oxytocin and nitric oxide (NO) all participate in the regulation of the preovulatory gonadotropin-releasing hormone (GnRH) surge. Recent studies from our laboratory have demonstrated that oxytocin induces dose-dependent release of GnRH from proestrous basal hypothalamus explants. The present studies were undertaken to determine whether norepinephrine could also stimulate GnRH release from similar explants, to identify the receptors responsible for this effect and to investigate interactions between norepinephrine, oxytocin and NO. Norepinephrine significantly stimulated GnRH release from proestrous basal hypothalamus explants, and coadministration of the ,1 -adrenergic antagonist prazosin blocked this effect. Combined administration of oxytocin and norepinephrine stimulated significantly more GnRH release than either drug alone, and this stimulation was blocked by inhibition of NO synthase, or by an oxytocin receptor antagonist. NO production was measured from the same samples using a modified Griess reaction. Oxytocin, but not norepinephrine, significantly increased NO production, as did norepinephrine and oxytocin in combination. Oxytocin receptor antagonist administration attenuated the stimulation of NO production by norepinephrine/oxytocin. These results demonstrate for the first time that oxytocin and norepinephrine dramatically stimulate GnRH release from basal hypothalamus explants harvested on the afternoon of proestrus, and indicate that this involves oxytocin receptor and NO-dependent mechanisms. [source] ,1 Adrenoreceptors Mediate The Stimulatory Effects of Oestrogen On Stress-Related Hypothalamic-Pituitary-Adrenal Activity in The Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2004V. Viau Abstract Variation in challenge-induced adrenocorticotropin hormone (ACTH) release over the oestrous cycle occurs in response to fluctuations in circulating concentrations of oestrogen and progesterone. However, how these ovarian steroids interact to regulate the principal ACTH cosecretagogues, corticotropin-releasing hormone (CRH) and arginine vasopressin is not understood. Here, we measured median eminence CRH and vasopressin content in intact cycling female rats, and in ovariectomized (OVX) females steroid-replaced in a manner that approximates the relative release patterns of oestrogen and progesterone seen over the oestrous cycle. Intact cycling females showed significantly higher median eminence CRH and vasopressin concentrations during proestrous and oestrous compared to the diestrous phase. In OVX rats, a single 10 µg injection of oestrogen failed to mimic this increase in median eminence CRH and vasopressin. However, this dose significantly elevated CRH and vasopressin content in OVX rats previously exposed to diestrous concentrations of oestrogen and progesterone. Moreover, oestrogen priming enhanced restraint-induced depletion of CRH and vasopressin from the median eminence, but only against a background of low oestrogen and progesterone replacement. Oestrogen-induced elevations in median eminence vasopressin (but not CRH) content were reduced by peripheral administration of the ,1 adrenoreceptor antagonist prazosin. Finally, plasma ACTH concentrations following central injection of the ,1 receptor agonist, phenylephrine, were significantly higher in rats during proestrous compared to diestrous. These results indicate that the stimulatory effect of oestrogen on both the expression and stress-induced release of ACTH cosecretagogues is exerted only against a background of low oestrogen and progesterone levels, and is mediated, in part, via the ,1 adrenoreceptor. [source] How important is stimulation of ,-adrenoceptors for melatonin production in rat pineal glands?JOURNAL OF PINEAL RESEARCH, Issue 4 2002V. A. Tobin The objective of this study was to determine the role of , -adrenoceptors in melatonin production by rat pineal gland. Pineal glands were isolated from adult male rats and maintained in organ baths. The perfusate was sampled every 5 min, stored, and later assayed for melatonin. Exposure to norepinephrine (10 ,M) or the , -adrenoceptor agonist orciprenaline (2,10 ,M) increased the glands' production of melatonin. The time courses of melatonin production in response to these agonists were unaffected by the rats' pretreatment in vivo with the , -adrenoceptor antagonist prazosin (2 mg/kg i.p., three times). Rats that had had their superior cervical ganglia removed were primed with either orciprenaline (2 mg/kg i.p) or both orciprenaline and phenylephrine (1 mg/kg i.p) 1 hr before decapitation. Exposure of the pineal glands from these rats to orciprenaline evoked melatonin release that was similar in each group. These results lend weight to the suggestion that the marked potentiation by , -adrenoceptor agonists of the stimulation of cAMP and N-acetyltransferase (NAT) by , -adrenoceptor agonists, demonstrated most readily in cultured glands or dispersed rat pinealocytes, does not carry over into significant augmentation of melatonin production in intact pineal glands. [source] Expression and functional characterization of the mt1 melatonin receptor from rat brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathwayJOURNAL OF PINEAL RESEARCH, Issue 3 2001Cirstin Blumenau Melatonin-sensitive receptors were expressed in Xenopus laevis oocytes following an injection of mRNA from rat brain. The administration of 0.1,100 ,mol/L melatonin to voltage-clamped oocytes activates calcium-dependent chloride currents via a pertussis toxin-sensitive G protein and the phosphoinositol pathway. To determine which melatonin receptor type (mt1, MT2, MT3) is functionally expressed in the Xenopus oocytes, we used (i) agonists and antagonists of different receptor types to characterize the pharmacological profile of the expressed receptors and (ii) a strategy of inhibiting melatonin receptor function by antisense oligonucleotides. During pharmacological screening administration of the agonists 2-iodomelatonin and 2-iodo-N-butanoyl-5-methoxytryptamine (IbMT) to the oocytes resulted in oscillatory membrane currents, whereas the administration of the MT3 agonist 5-methoxycarbonylamino-N-acetyltryptamine (GR135,531) exerted no detectable membrane currents. The melatonin response was abolished by a preceding administration of the antagonists 2-phenylmelatonin and luzindole but was unaffected by the MT3 antagonist prazosin and the MT2 antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT). In the antisense experiments, in the control group the melatonin response occurred in 45 of 54 mRNA-injected oocytes (83%). Co-injection of the antisense oligonucleotide, corresponding to the mt1 receptor mRNA, caused a marked and significant reduction in the expression level (13%; P<0.001). In conclusion, the results demonstrate that injection of mRNA from rat brain in Xenopus oocytes induced the expression of the mt1 receptor which is coupled to the phosphoinositol pathway. [source] Peptide YY administration into the posterior hypothalamic nucleus of the rat evokes cardiovascular changes by non-adrenergic, non-cholinergic mechanismsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2005J. R. Martin Summary 1 Microinjection of peptide YY (PYY) (0.23,2.3 nmol) into the posterior hypothalamic nucleus (PHN) of conscious rats evokes a dose-dependent pressor response and a bradycardia. 2 The increase in mean arterial pressure evoked by 2.3 nmol of PYY was not blocked by intravenous pretreatment with: (i) the nicotinic ganglionic receptor antagonist pentolinium (PENT, 10 mg kg,1) alone, or in combination with the muscarinic receptor antagonist methylatropine (MeATR, 1 mg kg,1); (ii) the ,1 -adrenoceptor antagonist prazosin (PRAZ, 0.2 mg kg,1); (iii) the V1 -vasopressin receptor antagonist [d(CH2)5Tyr(Me)]AVP (AVPX, 20 ,g kg,1); (iv) the combination of AVPX, PENT and MeATR; (v) the combination of PRAZ, AVPX, PENT, MeATR, and the ,2 -adrenoceptor antagonist yohimbine (0.3 mg kg,1); or (vi) the angiotensin II type 1 receptor antagonist ZD 7155 (1 mg kg,1). 3 Adrenal demedullation inhibited the PYY-evoked responses of drug-naïve rats, and rats pretreated with the combination of PENT, MeATR and AVPX. 4 Transection of the splanchnic nerve innervating the adrenal medullae attenuated the bradycardia, as did ZD 7155, but not the PYY-evoked pressor response. 5 Systemic pretreatment of rats with the neuropeptide Y1 receptor antagonist BIBP 3226 (1 mg kg,1) blocked the PYY-evoked cardiovascular changes, but not those evoked by microinjection of carbachol (5.5 nmol) into the PHN. 6 These results suggest that the cardiovascular changes evoked from the PHN by PYY requires the presence of the adrenal medullae, which are stimulated by: (i) a hormone to release an NPY-like substance that evokes the pressor response, and (ii) the splanchnic nerve to evoke the release of a substance that results in the bradycardia. [source] Pharmacological characterization of ,2 -adrenoceptor-mediated responses in pig nasal mucosaAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2003M. R. Corboz Summary 1 Pig nasal mucosal strips were incubated with ,-adrenoceptor antagonists followed by ,2 -adrenoceptor agonist concentration,response curves. 2 Contractions elicited by the ,2 -adrenoceptor agonists BHT-920 (pD2 = 6.16 ± 0.07), UK 14,304 (pD2 = 6.89 ± 0.13) and PGE-6201204 (pD2 = 7.12 ± 0.21) were blocked by the ,2 -adrenoceptor antagonist yohimbine (0.1 ,m). In contrast, the ,1 -adrenoceptor antagonist prazosin (0.03 ,m) had no effect on the BHT-920-, UK 14,304- and PGE-6201204-induced contractions, but blocked the contractile response to the ,1 -adrenoceptor agonist phenylephrine (pD2 = 5.38 ± 0.04) and the mixed ,1 - and ,2 -adrenoceptor agonist oxymetazoline (pD2 = 6.30 ± 0.22). 3 The ,2 -adrenoceptor antagonist yohimbine (0.01,0.1 ,m, pA2 = 8.04), ,2B/C -adrenoceptor antagonist ARC 239 (10 ,m, pKb = 6.33 ± 0.21), ,2A/C -adrenoceptor antagonist WB 4101 (0.3 ,m, pKb = 8.01 ± 0.24), ,2A -adrenoceptor antagonists BRL44408 (0.1 ,m, pKb = 6.82 ± 0.34) and RX 821002 (0.1 ,m, pKb = 8.31 ± 0.35), ,2C -adrenoceptor antagonists spiroxatrine (1 ,m, pKb = 7.32 ± 0.32), rauwolscine (0.1 ,m, pKb = 8.16 ± 0.14) and HV 723 (0.3 ,m, pKb = 7.68 ± 0.14) inhibited BHT-920-induced contractions in pig nasal mucosa. 4 The present antagonist potencies showed correlations with binding affinity estimates (pKi) obtained for these antagonists at the human recombinant ,2A - and ,2C -adrenoceptors (r = 0.78 and 0.83, respectively) and with binding affinity estimates (pKd) obtained in pig native ,2A - and ,2C -monoreceptor assays (r = 0.85 and 0.78, respectively). No correlation was observed for the ,2B -subtype. 5 In conclusion, contractile responses to phenylephrine, BHT-920, UK 14,304, PGE-6201204 and oxymetazoline indicate that ,1 - and ,2 -adrenoceptors are present and mediate vasoconstriction in pig nasal mucosa. Furthermore, correlation analysis comparing antagonist potency in pig nasal mucosa with affinities for human recombinant ,2 -adrenoceptors and native pig ,2 -adrenoceptors suggest that ,2A - and ,2C -adrenoceptor subtypes constrict pig nasal mucosa vasculature. [source] EFFECTS OF MELATONIN ON BLOOD PRESSURE IN STRESS-INDUCED HYPERTENSION IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2008Chun-Mei Xia SUMMARY 1Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. 2The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L) into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a competitive antagonist of melatonin MT1 and MT2 receptors, almost completely abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist 4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately 60%) the depressor effect of melatonin, whereas the MT3 receptor-selective antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin. 3Brain microdialysis was performed in the AHA and the rostral ventrolateral medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were detected by high-performance liquid chromatography combined with fluorescence detection. The results indicated that melatonin concentrations in the AHA were reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate release and increased GABA and taurine release in the RVLM, which were paralleled by a decrease in arterial pressure. 4The mRNA expression of MT2 in the AHA of SIHR was higher than that in normotensive control rats, whereas there was no significant difference in MT1 mRNA expressin between the two groups. 5The results of the present study suggest that both a decrease of melatonin and an increase in the MT2 receptor in the AHA are involved in the manifestation of stress-induced hypertension. Both MT1 and MT2 receptors participated in the antihypertensive effect of melatonin in the AHA. The antihypertensive effect of melatonin was related to the decreases in the excitatory amino acid glutamate and increases in the inhibitory amino acids taurine and GABA in the RVLM. [source] Tail arteries from chronically spinalized rats have potentiated responses to nerve stimulation in vitroTHE JOURNAL OF PHYSIOLOGY, Issue 2 2004Melanie Yeoh Patients with severe spinal cord lesions that damage descending autonomic pathways generally have low resting arterial pressure but bladder or colon distension or unheeded injuries may elicit a life-threatening hypertensive episode. Such episodes (known as autonomic dysreflexia) are thought to result from the loss of descending baroreflex inhibition and/or plasticity within the spinal cord. However, it is not clear whether changes in the periphery contribute to the exaggerated reflex vasoconstriction. The effects of spinal transection at T7,8 on nerve- and agonist-evoked contractions of the rat tail artery were investigated in vitro. Isometric contractions of arterial segments were recorded and responses of arteries from spinalized animals (,spinalized arteries') and age-matched and sham-operated controls were compared. Two and eight weeks after transection, nerve stimulation at 0.1,10 Hz produced contractions of greater force and duration in spinalized arteries. At both stages, the ,-adrenoceptor antagonists prazosin (10 nm) and idazoxan (0.1 ,m) produced less blockade of nerve-evoked contraction in spinalized arteries. Two weeks after transection, spinalized arteries were supersensitive to the ,1 -adrenoceptor agonist phenylephrine, and the ,2 -adrenoceptor agonist, clonidine, but 8 weeks after transection, spinalized arteries were supersensitive only to clonidine. Contractions of spinalized arteries elicited by 60 mm K+ were larger and decayed more slowly at both stages. These findings demonstrate that spinal transection markedly increases nerve-evoked contractions and this can, in part, be accounted for by increased reactivity of the vascular smooth muscle to vasoconstrictor agents. This hyper-reactivity may contribute to the genesis of autonomic dysreflexia in patients. [source] Rho kinase inhibitors reduce neurally evoked contraction of the rat tail artery in vitroBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2005Melanie Yeoh The effects of Rho kinase inhibitors (Y27632, HA-1077) on contractions to electrical stimulation and to application of phenylephrine, clonidine or ,,, -methylene adenosine 5,-triphosphate (,,, -mATP) were investigated in rat tail artery in vitro. In addition, continuous amperometry and intracellular recording were used to monitor the effects of Y27632 on noradrenaline (NA) release and postjunctional electrical activity, respectively. Y27632 (0.5 and 1 ,M) and HA-1077 (5 ,M) reduced neurally evoked contractions. In contrast, the protein kinase C inhibitor, Ro31-8220 (1 ,M), had little effect on neurally evoked contraction. In the absence and the presence of Y27632 (0.5 ,M), the reduction of neurally evoked contraction produced by the , -adrenoceptor antagonists prazosin (10 nM) and idazoxan (0.1 ,M) was similar. The P2-purinoceptor antagonist, suramin (0.1 mM), had no inhibitory effect on neurally evoked contraction in the absence or the presence of Y27632 (1 ,M). In the presence of Y27632, desensitization of P2X-purinoceptors with ,,, -mATP (10 ,M) increased neurally evoked contractions. Y27632 (1 ,M) and H-1077 (5 ,M) reduced sensitivity to phenylephrine and clonidine. In addition, Y27632 reduced contractions to ,,, -mATP (10 ,M). Y27632 (1 ,M) had no effect on the NA-induced oxidation currents or the purinergic excitatory junction potentials and NA-induced slow depolarizations evoked by electrical stimulation. Rho kinase inhibitors reduce sympathetic nerve-mediated contractions of the tail artery. This effect is mediated at a postjunctional site, most likely by inhibition of Rho kinase-mediated ,Ca2+ sensitization' of the contractile apparatus. British Journal of Pharmacology (2005) 146, 854,861. doi:10.1038/sj.bjp.0706377 [source] ,1 -Adrenoceptor effects mediated by protein kinase C , in human cultured prostatic stromal cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2003A Preston We have investigated the effects of ,1 -adrenoceptor stimulation upon contractility, Ca2+ influx, inositol phosphate production, and protein kinase C (PKC) translocation in human cultured prostatic stromal cells (HCPSC). The ,1 -adrenoceptor selective agonist phenylephrine elicited contractile responses of HCPSC, i.e. a maximal cell shortening of 45±6% of initial cell length, with an EC50 of 1.6±0.1 ,M. The ,1 -adrenoceptor selective antagonists prazosin (1 ,M) and terazosin (1 ,M) both blocked contractions to phenylephrine (10 ,M). The L-type calcium channel blocker nifedipine (10 ,M), and the PKC inhibitors Gö 6976 (1 ,M) and bisindolylmaleimide (1 ,M) also inhibited phenylephrine-induced contractions. Phenylephrine caused a concentration dependent increase in inositol phosphate production (EC50 119±67 nM). This response was blocked by terazosin (1 ,M). Phenylephrine caused the translocation of the PKC , isoform, but not the ,, ,, ,, , or , isoforms, from the cytosolic to the particulate fraction of HCPSC, with an EC50 of 5.7±0.5 ,M. In FURA-2AM (5 ,M) loaded cells, phenylephrine elicited concentration dependent increases in [Ca2+]i, with an EC50 of 3.9±0.4 ,M. The response to phenylephrine (10 ,M) was blocked by prazosin (1 ,M), bisindolymaleimide (1 ,M), and nifedipine (10 ,M). In conclusion, this study has shown that HCPSC express functional ,1 -adrenoceptors, and that the intracellular pathways responsible for contractility may be largely dependent upon protein kinase C activation and subsequent opening of L-type calcium channels. British Journal of Pharmacology (2003) 138, 218,224. doi:10.1038/sj.bjp.0705021 [source] | |||||||||||||