Role of L-type Ca2+ channel in PACAP-induced adrenal catecholamine release in vivo

1997 ◽  
Vol 273 (4) ◽  
pp. R1339-R1345 ◽  
Author(s):  
Guoju Geng ◽  
Rania Gaspo ◽  
Fethi Trabelsi ◽  
Nobuharu Yamaguchi

The aim of the present study was to investigate whether the dihydropyridine-sensitive L-type Ca2+ channel is operative in adrenal catecholamine (CA) secretion induced by a novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography method. All drugs tested were locally infused into the left adrenal gland via the left adrenolumbar artery. PACAP, with the isoform consisting of 27 (PACAP-27) and 38 (PACAP-38) amino acid residues, significantly increased CA output in a dose-dependent manner, with doses ranging from 5 to 500 ng and 7 to 700 ng, respectively. However, the amplitude of epinephrine response to PACAP-27 was three times greater than that obtained with PACAP-38 at the highest dose tested. In a separate group, a single dose of PACAP-27 (50 ng) induced highly reproducible CA responses when the same dose was repeated with an interval of 35 min. In dogs treated with nifedipine (50 μg), 5 min before the second administration of PACAP-27, the net CA response was significantly inhibited by ∼50% compared with that obtained in the presence of vehicle. A similar CA response to BAY K 8644 (5 μg) was completely abolished by the same dose of nifedipine. The present results indicate that both PACAP-27 and PACAP-38 have the direct local secretagogue effect on the adrenal medulla in vivo and that CA responses to PACAP-27 were greater than those observed with PACAP-38 at equivalent mole doses. The study suggests that the dihydropyridine-sensitive L-type Ca2+ channel is functionally involved in PACAP-induced adrenal CA secretion in the canine adrenal medulla in vivo.

1997 ◽  
Vol 272 (4) ◽  
pp. R1290-R1297 ◽  
Author(s):  
N. Yamaguchi

The present study was designed to test whether endothelin (ET) A and/or B receptors in the adrenal medulla are functionally involved in ET-1-induced catecholamine (CA) release in anesthetized dogs. ET-1 was locally infused into the gland via the left adrenolumbar artery. Plasma CA in adrenal venous and aortic blood was determined by a high-performance liquid chromatography method. In the control group, the local infusion of ET-1 (0.5 microg, 0.4 microM) resulted in a significant increase in CA output. In the presence of a low dose of BQ-123 (5 microg, 16.4 microM), the ET-1-induced CA response was significantly attenuated by approximately 80%. With a high dose of BQ-123 (50 microg, 164 microM), the CA response was further blocked by approximately 95%. This inhibition was significantly greater than that obtained with the low dose of BQ-123. By contrast, a low dose of BQ-788 (5 microg, 15.1 microM) did not significantly affect the CA response. With a high dose of BQ-788 (50 microg, 151 microM), the CA response was only partially inhibited by approximately 70%. The results indicate that BQ-123 significantly inhibited ET-1-induced adrenal CA release in a dose-dependent manner. With the low doses, the CA response was markedly inhibited by BQ-123 but remained unchanged in the presence of BQ-788. Moreover, the high dose of BQ-123 virtually abolished the CA response, whereas BQ-788 failed to do so within the dose range tested. The present study suggests that the ET(A) receptor may play a predominant role in mediating the ET-1-induced CA secretion in the canine adrenal gland in vivo, although the possible involvement of the ET(B) receptor could not completely be excluded under the present experimental conditions.


2021 ◽  
Vol 16 (9) ◽  
pp. 1934578X2110350
Author(s):  
Lijun Cheng ◽  
Yang Deng

Gastrodin (GAS) and its aglycone, p-hydroxybenzyl alcohol (HBA), are both bioactive compounds extracted from Gastrodia elata Blume (GEB). In the current Chinese pharmacopoeia, they are regarded as quality control markers for GEB. In this study, we developed a high-performance liquid chromatography method coupled with a diode array detector to quantify GAS and HBA concentrations in plasma following oral ingestion by rats. For the first time, GAS was detected in vivo after HBA administration. GAS and HBA both had similar pharmacological effects, but the influence of the glucose moiety resulted in different pharmacokinetic characteristics. In this study, the effects of GAS and HBA at different administration durations were investigated in zebrafish larvae. These compounds were found to induce a sedative effect but had different onset times. In conclusion, a biotransformation of HBA to GAS could be observed in the rats. This may be a new insight into the pharmacokinetic characteristics of these bioactive compounds and also relates to the different ways in which they take effect.


1995 ◽  
Vol 269 (2) ◽  
pp. R287-R293 ◽  
Author(s):  
N. Yamaguchi

The aim of the present study was to investigate if either dihydropyridine-sensitive L-type Ca2+ channels or cholinergic receptor-mediated mechanisms are implicated in endothelin-1 (ET)-induced adrenal catecholamine (CA) secretion in anesthetized dogs. ET was locally administered to the left adrenal gland via the left adrenolumbar artery. Plasma CA concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography method. In the control group, local infusion (1 min, 0.5 ml/min) of ET (the fixed total dose of 0.5 microgram given to the gland or approximately 0.0197 microgram/kg of body weight) resulted in a sharp increase in the basal CA output, followed by a rapid decline, and a relatively slow secondary response lasted over a period of 15-30 min. In the second group treated with nifedipine (5 micrograms or approximately 0.207 microgram/kg) similarly administered 10 min before ET infusion, the ET-induced first steep increase in CA output was significantly attenuated by approximately 75% (P < 0.05, n = 6). In dogs similarly receiving either pentolinium (1 mg or approximately 0.041 mg/kg) or atropine (0.5 mg or approximately 0.018 mg/kg), the ET-induced CA response remained unchanged. The results indicate that ET-induced adrenal CA release was largely mediated by the activation of dihydropyridine-sensitive L-type Ca2+ channels. Furthermore, neither nicotinic nor muscarinic receptors were functionally implicated in the CA response to ET. The study suggests the existence of noncholinergic mechanisms involved in the secretory action of ET on the adrenal medulla in the dog in vivo.


Author(s):  
Rajasekhar Reddy Alavala ◽  
Prathusha Katahala ◽  
Ganapathi Thipparapu ◽  
Umasankar Kulandaivelu ◽  
Shireesha Boyapati ◽  
...  

Objective: Tacrine is a potent acetylcholine esterase inhibitor (AChEI), and curcumin has been recently proven to possess AChEI, amyloid β aggregation inhibitory activity in addition to its diverse pharmacodynamic nature. Tacrine undergoes biological transformation by cytochrome P450 (CYP 1A2) to a hydroxy metabolite, which is hepatotoxic. Curcumin is known for its inhibitory nature for various metabolic enzymes along with CYP1A2. The present study was undertaken to evaluate the influence of curcumin on the disposition kinetics of tacrine and to assess its impact on dosage regimen.Methods: It was hypothesized that the simultaneous administration of curcumin and tacrine can minimize the toxicity along with increased absorption of tacrine and curcumin into the biological system during the treatment of Alzheimer’s patients.Results and Discussion: Hence, an attempt was made to develop a simple, precise, accurate, and cost-effective reversed-phase high-performance liquid chromatography method for simultaneous determination of curcumin and tacrine and also to estimate the effect of curcumin on absorption of tacrine, in rat plasma.Conclusion: Concomitant administration of curcumin with tacrine improved the parameters such as Cmax and AUC, which indicates that the curcumin would improve the absorption of tacrine.


2008 ◽  
Vol 52 (9) ◽  
pp. 3047-3051 ◽  
Author(s):  
Stephanie J. Wallace ◽  
Jian Li ◽  
Craig. R. Rayner ◽  
Kingsley Coulthard ◽  
Roger L. Nation

ABSTRACT Colistin methanesulfonate (CMS) has the potential to hydrolyze in aqueous solution to liberate colistin, its microbiologically active and more toxic parent compound. While conversion of CMS to colistin in vivo is important for bactericidal activity, liberation of colistin during storage and/or use of pharmaceutical formulations may potentiate the toxicity of CMS. To date, there has been no information available regarding the stability of CMS in pharmaceutical preparations. Two commercial CMS formulations were investigated for stability with respect to colistin content, which was measured by a specific high-performance liquid chromatography method. Coly-Mycin M Parenteral (colistimethate lyophilized powder) was stable (<0.1% of CMS present as colistin) for at least 20 weeks at 4°C and 25°C at 60% relative humidity. When Coly-Mycin M was reconstituted with 2 ml of water to a CMS concentration of 200 mg/ml for injection, Coly-Mycin M was stable (<0.1% colistin formed) for at least 7 days at both 4°C and 25°C. When further diluted to 4 mg/ml in a glucose (5%) or saline (0.9%) infusion solution as directed, CMS hydrolyzed faster at 25°C (<4% colistin formed after 48 h) than at 4°C (0.3% colistin formed). The second formulation, CMS Solution for Inhalation (77.5 mg/ml), was stable at 4°C and 25°C for at least 12 months, as determined based on colistin content (<0.1%). This study demonstrated the concentration- and temperature-dependent hydrolysis of CMS. The information provided by this study has important implications for the formulation and clinical use of CMS products.


2011 ◽  
Vol 5 (4) ◽  
Author(s):  
Nichakorn Sukasame ◽  
Narumon Nimnoo ◽  
Tan Suwandecha ◽  
Teerapol Srichana

AbstractBackground: Salbutamol is a βObjective: Evaluate the relationship of in vitro particle size characteristics and pharmacodynamics of formulations of inhaled salbutamol dry powder.Methods: Three formulations contained micronized salbutamol and a lactose carrier with different size ranges (40- 80, 20-40, and 10-20 μm for formulations 1, 2, and 3, respectively). Following formulation of the drug, resultant powders were characterized using scanning electron microscopy and the aerosolization performance determined using an Andersen Cascade Impactor analysis. A high-performance liquid chromatography method was used for measuring the salbutamol drug content. The in vivo pharmacodynamics of the formulations was monitored in 12 healthy and 12 asthmatic volunteers.Results: The percentage of the fine particle fractions (FPF) for formulations 1, 2, and 3 were 24.87±0.52%, 33.82±3.80%, and 41.50±2.86%, respectively. The mass median aerodynamic diameters (MMAD) were around 3 μm for all formulations. The pharmacodynamic parameters, forced vital capacity (FVC), forced expiratory volume in one second (FEVConclusion: The formulations of salbutamol dry powder aerosols with a fine lactose carrier produced a high deposition in the lower regions of the respiratory tract. Although the FEF


1999 ◽  
Vol 276 (1) ◽  
pp. R162-R170 ◽  
Author(s):  
Stéphane Lamouche ◽  
Daniel Martineau ◽  
Nobuharu Yamaguchi

The aim of the present study was to investigate whether pituitary adenylate cyclase-activating polypeptide-(1—27) (PACAP27) can modulate the adrenal catecholamine (CA) secretion induced by splanchnic nerve stimulation (SNS) and by exogenous acetylcholine (ACh) in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were quantified by a high-performance liquid chromatography coupled with electrochemical detection. Adrenal venous blood flow was measured by gravimetry. Local infusion of PACAP27 (0.5, 5, and 50 ng) to the left adrenal gland via the adrenolumbar artery resulted in an increase in CA output, reaching a significant level at the highest dose tested. Either direct SNS (2 Hz) or local infusion of ACh (0.5 μg) to the left adrenal gland produced significant increases in CA output to an extent similar to that obtained with 50 ng of PACAP27 alone. In the presence of PACAP27 (50 ng), CA responses to either SNS or exogenous ACh were significantly potentiated by approximately four- and sixfold, respectively, compared with those obtained in response to each stimulus alone. However, the enhanced CA responses to ACh were not significantly different from those to SNS. The results indicate that the increase in adrenal CA secretion, induced by either direct SNS or exogenous ACh, is synergistically enhanced by PACAP27. The study suggests that the enhanced CA secretion may result from the activation of a PACAP-mediated facilitatory mechanism(s) localized presumably at the postsynaptic level in the canine adrenal medulla in vivo, although the possible involvement of presynaptic mechanisms cannot completely be ruled out in the present study.


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