Dopamine HCl Research Articles

Characterization and in vitro evaluation of melanin nanoparticles as an oral drug delivery system: Studies using Caco-2 cell model and molecular dynamics simulations

Interest has been shown in the use of melanin nanoparticles (MNPs) for drug delivery applications. This study investigates the potential use of MNPs as an oral drug delivery system. The toxicity and cellular uptake of MNPs via intestinal barrier were evaluated using the Caco-2 cell model. Doxorubicin (DOX) was selected as a representative low bioavailability drug. The DOX-release profile of drug-loaded MNPs and molecular dynamic (MD) simulation were investigated at different pH. Our results demonstrated that MNPs synthesized from dopamine HCl are suitable as nanocarriers, presenting as monodisperse particles at mean size <300 nm. MNPs at size 89, 156, 268 nm at 3.13–50 μg/mL showed a high biocompatibiltity with Caco-2 cells, since no significant changes in %cell viability, reactive oxygen species, mitochondria membrane potential, and inflammatory cytokine were observed. The TEM results exhibited cellular internalization of MNPs into Caco-2 cells. The loading capacity (LC) and entrapment efficiency (EE) of DOX-loaded MNPs were 13.3 ± 2.7 % and 30.0 ± 3.6 %, respectively. DOX-loaded MNPs possessed a pH-dependent drug release profile. At pH 1.2, the amount of liberated DOX was 1.6- and 3.8-fold increase in comparison to pH 5 and 7.4, respectively. MD simulation clearly demonstrated that the binding affinity between polydopamines of MNPs and DOX molecules was weaker at the lower pH. These results thus support the potential use of MNPs as an oral drug delivery system particularly for drugs used in cancer treatment.

Design, optimization, and evaluation of methotrexate loaded and albumin coated polymeric nanoparticles

Methotrexate is a potent anticancer drug whose strong efflux is facilitated by the brain’s efflux transporter. As an efflux transporter blocker, albumin increased the drug’s concentration in the brain. Methotrexate-loaded nanoparticles were produced by evaporating the emulsification fluid. Improvements and analyses were made to the following aspects of the generated nanoparticles: size, polydispersity, zeta potential, entrapment efficiency, percentage yield, scanning electron microscopy, in vitro drug release studies, and sterilization. The particle size was determined to be in the nano range, and homogeneity of particle size was suggested by a low polydispersity index result. Particle diameters of 168 nm were observed in the F5 preparation, and zeta potential values of −1.5 mV suggested that the preparation produced adequate repulsive interactions between the nanoparticles. Albumin and dopamine HCl were employed to coat the methotrexate-loaded nanoparticles to guarantee that the brain received an adequate amount of them. The homogeneity of albumin coated nanoparticles was demonstrated by the low% PDI values of 0.129 and 0.122 for albumin coated nanoparticles (MNPs-Alb) and polymerized dopamine HCl and albumin coated nanoparticles (MNPs-PMD-Alb), respectively. After 48 h of incubation, the cell viability measured at the same drug concentration (5 mg) decreased for the F5, albumin coated nanoparticles, polymerized dopamine HCl coated nanoparticles, and polymerized dopamine HCl and albumin coated nanoparticles, respectively. Our primary findings demonstrate that the albumin nanoparticles containing methotrexate are designed to deliver the drug gradually. With minimal cytotoxicity, the intended preparation might give the brain an appropriate dosage of methotrexate.

Characterization and HPLC Method Validation for Determination of Dopamine Hydrochloride in Prepared Nano Particles and Pharmacokinetic Application

The emotional control monoamines neurotransmitter catecholamine group of chemicals is dopamine. It has been described and recognized that a lack of dopamine containing neurons contributes to neurological issues, such as Parkinsonism. Due to the incapability of dopamine HCl to cross the blood brain barrier, the advanced novel drug delivery of dopamine HCl is performed in the form of nano structure lipid carrier system (NLC-DOPA) to bypass the blood brain barrier using intranasal route of administration with improved compliance bioavailability and less side effect. The NLC-DOPA was prepared by the high pressure homogenizer ultra-probe sonicator and characterized by the particle size analyzer, zeta potential, transmission electron microscopy (TEM) and X-Ray diffraction (XRD). The determination of dopamine hydrochloride in formulation was evaluated by drug entrapment efficiency further it is validated by analytical method development using high performance liquid chromatography (HPLC) with C18 ODS column and 0.05 M KH2PO4 buffer pH 2.5 and Methanol (90:10) along with retention time 4.872 min at 280 nm wavelength. The method was validated for dopamine HCl in formulation with linearity, precision and recovery analysis. The study was shown that method was easy, rapid, accurate, specific and precise for quality analysis of dopamine HCl in NLC-DOPA formulation. The validated method of HPLC was further used for the biological application in term of the pharmacokinetic study to find out the concentration of drug in blood as well as brain. The pharmacokinetic parameters were calculated with help of the software PK solver 2.0 to determine the maximum concentration (Cmax), Maximum time (Tmax), Elimination half life (t1/2), Area under the curve (AUC0-t), volume of distribution (Vz/F_obs) and Clearance (Cl/F_obs) of all groups of animals (n=3). The study showed that the NLC-DOPA was producing a sustained and controlled release in appropriate amount of drug through intranasal bypass delivery into brain.

Binding studies of dopamine HCl drug with the mixed {sodium bis(2-ethylhexyl) sulfosuccinate + sodium dodecylsulfate} micelles: Physicochemical, spectroscopic, calorimetric and computational approach

Taking into consideration the importance of dopamine HCl as neurotransmitter in controlling central nervous system activities, the studies of binding interactions of dopamine HCl drug with micellar system (imitator of biomembranes) have been conducted by utilizing experimental as well as computational techniques. The systematic knowledge of physicochemical, spectroscopic and calorimetric properties is helpful to understand the physiological actions of biologically active additives in the living organisms. Therefore, mixed aggregation behavior of sodium bis(2-ethylhexyl) sulfosuccinate, AOT and sodium dodecylsulfate, SDS has been explored at diverse mole fractions of AOT, αAOT = 0.25, 0.39 and 0.50 in (1, 2 and 3) × 10−3 mol kg−1 dopamine HCl(aq) solutions by employing different techniques. From conductivity studies, the thermodynamic parameters (∆G°m, ∆H°m and ∆S°m), the molecular interaction parameter (βint) and the excess Gibbs free energy of micellization (∆Gmex) were ascertained at T = (298.15, 308.15, and 318.15) K. Isentropic compressibility (κs), partial specific volume (φv) and partial specific isentropic compressibility (φκ) parameters were computed from the density and sound velocity studies. Binding constant (Kb) and standard Gibbs free energy of binding (∆Gbο) have been evaluated from UV–visible absorption studies for dopamine HCl(aq) solutions at all the studied mole fractions of surfactant mixtures. Through dynamic light scattering (DLS) measurements, the hydrodynamic diameters (Dh) of mixed micellar aggregates have been acquired. Isothermal titration calorimetric (ITC) studies were executed to obtain the values of partitioning constant / binding constant (K), standard molar enthalpy of binding (ΔrHᴼ), standard molar entropy of binding (ΔrSᴼ), and stoichiometry of partitioning / binding (n) of drug with micellar system. Through density functional theory (DFT) calculations, the band gap between HOMO and LUMO for the dopamine-HCl bound mixed micelle system, and interactive features have been obtained. Aforementioned studies favor the supremacy of hydrophilic-hydrophilic / ionic and electrostatic interactions causing the binding among the hydrophilic / ionic groups of dopamine HCl (−OH, H+, Cl−), AOT (–SO3−, –OCO, Na+), and SDS (–OSO3−, Na+).

Synthesis and validation of ultrasensitive stripping voltammetric sensor based on polypyrrole@ZnO/Fe3O4 core-shell nanostructure for picomolar detection of artesunate and dopamine drugs.

A stripping voltammetric sensor for ultrasensitive detection of artesunate (ART) and dopamine HCl (DA) has been successfully developed using a Ppy@ZnO/Fe3O4 core-shell nanocomposite ([PZM])-modified carbon paste sensor (MCPS). Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, dynamic light scattering, Brunauer-Emmett-Teller surface area method, and high-resolution transmission electron microscopy were used to characterize the physicochemical properties of the nanomaterials. Noteworthily, the morphology of [PZM] reveals a spherical core-shell nanostructure with an increase in the average diameter range of 20-37.5 nm (specific surface area (SSA) of 28.5 m2 g-1 (0.0247 cm3 g-1)) when compared with the average diameter range 7.5-15.7 nm (SSA of 5.43 m2 g-1 (0.0111 cm3 g-1)) of ZnO/Fe3O4[ZM]. The [PZM] MCPS provided the best electroactive surface area (0.078 cm2) and the least electrocatalytic activity (Rst = 370 Ω). Furthermore, the MCPS showed low detection limits (LODs) of 0.092 pg mL-1 (0.24 pM) and 0.0046 pg mL-1 (0.03 pM) for ART and DA, respectively. Moreover, LODs were found to be 0.029 pg mL-1 (0.75 pM) and 0.014 pg mL-1 (0.09 pM) for ART mixed with 0.7 pM of DA (ART1) and DA in the presence of 2.0 pM of ART drug (DA1), respectively. In addition, the MCPS revealed a proper repeatability, reproducibility, and storage stability (93.5-90.48%). During the routine analysis, the [PZM] MCPS detected ART and DA concentrations in human urine, without interference.

Development of alginate and gelatin-based pleural and tracheal sealants

Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges are requirements for adherence, high strength and elasticity, dynamic durability, appropriate biodegradability, and lack of cell or systemic toxicity. We designed and evaluated two sealant materials comprised respectively of alginate methacrylate and of gelatin methacryloyl, each functionalized by conjugation with dopamine HCl. Both compounds are cross-linked into easily applied as pre-formed hydrogel patches or as in situ hydrogels formed at the wound site utilizing FDA-approved photo-initiators and oxidants. Material testing demonstrates appropriate adhesiveness, tensile strength, burst pressure, and elasticity with no significant cell toxicity in vitro assessments. Air-leak was absent after sealant application to experimentally-induced injuries in ex-vivo rat lung and tracheal models and in ex vivo pig lungs. Sustained repair of experimentally-induced pleural injury was observed for up to one month in vivo rat models and for up to 2 weeks in vivo rat tracheal injury models without obvious air leak or obvious toxicities. The alginate-based sealant worked best in a pre-formed hydrogel patch whereas the gelatin-based sealant worked best in an in situ formed hydrogel at the wound site thus providing two potential approaches. These studies provide a platform for further pre-clinical and potential clinical investigations. Statement of significancePneumothorax and pleural effusions resulting from trauma and a range of lung diseases and critical illnesses can result in lung collapse that can be immediately life-threatening or result in chronic leaking (bronchopleural fistula) that is currently difficult to manage. This leads to significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. We have developed sealants originating from alginate and gelatin biomaterials, each functionalized by methacryloylation and by dopamine conjugation to have desired mechanical characteristics for use in pleural and tracheal injuries. The sealants are easily applied, non-cytotoxic, and perform well in vitro and in vivo model systems of lung and tracheal injuries. These initial proof of concept investigations provide a platform for further studies.

Electrochemical Sensing of Dopamine Using Onion-like Carbons and Their Carbon Nanofiber Composites

This work describes the electrochemical detection of dopamine in samples (pure raw materials as well as pharmaceutical formulation) using onion-like carbon (OLC) and its carbon nanofiber composites (OLC-CNF). The OLC-CNF and precursor materials (polyacrylonitrile (PAN) fiber and OLC-PAN) were synthesized using electrospinning process. The morphologies of the samples were obtained using scanning electron microscopy (SEM) while surface area and porosity were determined using the Brunauer–Emmett–Teller (BET) analysis. OLC gave the best surface area (279 m2 g−1) and highest pore volume (1.2 cm3 g−1). To determine electrochemical sensing properties, the materials were drop-cast on the glassy carbn electrode (GCE). The electron transfer properties decrease as follows: OLC > OLC-PAN > OLC-CNF > PAN, suggesting that OLC is the most conductive materials. The modified GCE were used as sensors for the dopamine using electrochemical techniques such as cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS). OLC and OLC-CNF gave comparable electrocatalytic activities in terms of sensitivity and limit of detection (OLC 1.23 μM and sensitivity of 0.74 μA/μM, and OLC-CNF 1.42 μM, 0.31 μA/μM). The high performance of OLC is attributed to its advantageous nanoparticulate nature and high conductivity. Both sensors (OLC and OLC-CNF) could be reliably used in the assay of dopamine raw material and its pharmaceutical formulation, dopamine HCl injection (Rotexmedica®). One of the key fndings here is that the incorporation of the CNF into the OLC does not significantly impact on its inherent tensile strain that defines its electrochemical performance.

Transferrin Functionalized Liposomes Loading Dopamine HCl: Development and Permeability Studies across an In Vitro Model of Human Blood-Brain Barrier.

The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson’s disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration–rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(poly(ethylene glycol)-2000)]. The physical features of the prepared liposomes were established with successive determination of their endothelial permeability across an in vitro model of the blood-brain barrier, constituted by human cerebral microvascular endothelial cells (hCMEC/D3). Functionalized dopamine-loaded liposomes with encapsulation efficiency more than 35% were made with sizes in a range around 180 nm, polydispersity indices of 0.2, and positive zeta potential values (+7.5 mV). Their stability and drug release kinetics were also evaluated. The apparent permeability (Pe) values of encapsulated dopamine in functionalized and unfunctionalized liposomes showed that transferrin functionalized nanocarriers could represent appealing non-toxic candidates for brain delivery, thus improving benefits and decreasing complications to patients subjected to L-dopa chronical treatment.

Electrochemical behavior of dopamine on La@C82-COOH/C60-COOH/C70-COOH modified electrodes

ABSTRACTThree kinds of carboxyfullerenes, La@C82-COOH, C60-COOH and C70-COOH, were used to modify gold electrodes. The electrochemical behavior of dopamine (DA) at the carboxyfullerenes modified electrodes was studied using the cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods. The C70-COOH modified electrodes performed the best among them. Under the optimal conditions, linear CV and DPV responses to DA concentration from 1 μmol/L to 13 μmol/L were observed, and the detection limit of DA was 1×10−2 μmol/L in the presence of 10 μmol/L uric acid (UA). The practical analytical utilities of the C70-COOH modified electrodes were demonstrated by the determination of DA HCl in the real samples of dopamine hydrochloride injection (DHI). Moreover, the modified electrodes exhibited good reproducibility and sensitivity, demonstrating its feasibility for analytical purpose.

Elucidating the Structure of Poly(dopamine)

Herein we propose a new structure for poly(dopamine), a synthetic eumelanin that has found broad utility as an antifouling agent. Commercially available 3-hydroxytyramine hydrochloride (dopamine HCl) was polymerized under aerobic, aqueous conditions using tris(hydroxymethyl)aminomethane (TRIS) as a basic polymerization initiator, affording a darkly colored powder product upon isolation. The polymer was analyzed using a variety of solid state spectroscopic and crystallographic techniques. Collectively, the data showed that in contrast to previously proposed models, poly(dopamine) is not a covalent polymer but instead a supramolecular aggregate of monomers (consisting primarily of 5,6-dihydroxyindoline and its dione derivative) that are held together through a combination of charge transfer, π-stacking, and hydrogen bonding interactions.

Mutually opposite effects of dopamine·HCl and chlorpromazine· HCl on the thickness of liposomal lipid bilayers

The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of dopamine.HCl (DA) and chlorpromazin.HCl (CPZ). Radiationless energy transfer from the surface fluorescent probe, 1-anilinonaphthalene-8-sulfonic acid, to the hydrophobic fluorescent probe, bispyrenylpropane (Py-Py), was used to examine the effects of DA and CPZ on the thickness (D) of the liposomal lipid bilayers prepared with total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from neuronal membranes. The thickness (D) of intact SPMVTL and SPMVPL (37 degrees C, pH 7.4) were 0.914 +/- 0.010 and 0.886 +/- 0.009 (arbitrary units, n = 5), respectively. DA decreased the thickness of both SPMVTL and SPMVPL in a dose-dependent manner with a significant decrease in thickness observed even at 40 x 10(-9) M and 40 x 10(-9) M, respectively. On the other hand, CPZ increased the thickness of both SPMVTL and SPMVPL in a dose-dependent manner with a significant increase in thickness observed even at 35 x 10(-5) M and 35 x 10(-5) M, respectively. The sensitivities to the decreasing and increasing effect of the membrane lipid bilayers thickness by DA and CPZ, respectively, differed according to the liposomes in descending order of SPMVPL and SPMVTL. The decreasing and increasing action of DA and CPZ, respectively, on the membrane thickness had many effects that may be responsible for the dopaminergic receptor-DA and -CPZ interaction as well as the protein-lipid interaction.

Synthesis of dopamine and l-DOPA-α-glycosides by reaction with cyclomaltohexaose catalyzed by cyclomaltodextrin glucanyltransferase

Dopamine–HCl and l-DOPA-α-glycosides were prepared by reaction with cyclomaltohexaose, catalyzed by Bacillus macerans cyclomaltodextrin glucanyltransferase. The reaction gave maltodextrins attached to dopamine and l-DOPA; the maltodextrins were trimmed by reactions with glucoamylase and β-amylase to produce α-glucosyl- and α-maltosyl-glycosides, respectively. The glucoamylase- or β-amylase-treated dopamine- and l-DOPA-α-glycosides were fractionated and purified by BioGel P-2 gel-filtration column chromatography and preparative descending paper chromatography. Analysis by MALDI-TOF mass spectrometry and one- and two-dimensional NMR showed that the purified glycosides of dopamine and l-DOPA were glycosylated at the hydroxyl groups of positions 3 and 4 of the catechol ring. The major product was found to be 4-O-α-glycopyranosyl l-DOPA, and it was shown to be more resistant to oxidative tolerance experiments, involving hydrogen peroxide and ferrous ion, than l-DOPA. l-DOPA-α-glycosides are possibly more effective substitutes for l-DOPA in treating Parkinson’s disease in that they are more resistant to oxidation and methylation, which renders l-DOPA ineffective and deleterious.

Third‐Degree Atrioventricular Block in a Horse Secondary to Rattlesnake Envenomation

Third‐Degree Atrioventricular Block in a Horse Secondary to Rattlesnake Envenomation

Comparison of Long-Term Perifused Pars intermedia of Anolis carolinensis, Rana pipiens and Hyla chrysoscelis: Their Responses to Dopamine

Pituitary pars nervosa-pars intermedia of Anolis carolinensis, Rana pipiens and Hyla crysoscelis were perifused with synthetic medium 199 for up to 35 h. The pre- and post-perifused tissues were examined by electron microscopy. No neuronal endings were found in Anolis tissue, but both Rana and Hyla had occasional synaptic end bulbs, which remained visible in the post-perifused tissue, although the synaptic vesicles appeared to cluster in the center of the end bulbs. Exposure to dopamine HCl from 10^–8 to10^–5M had little effect on Anolis pituitary but inhibited Rana and Hyla pituitaries from releasing skin-darkening substances. The skin-darkening substances, presumably derivatives of the proopiomelanocortin molecule, were assayed on Anolis skin. No dose-dependent responses to dopamine were seen at the concentrations used. We saw the possibility of a short-loop feedback.

Compatibility of tirofiban HCl with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride during simulated Y-site administration.

To study the compatibility of tirofiban HCl injection 0-05 mg/ml with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride infusion solutions during simulated Y-site administration. Tirofiban HCl, dopamine HCl, famotidine, lidocaine HCl and potassium chloride infusions were each prepared from their respective concentrates as per current clinical preparation instructions in both 0.9% sodium chloride and 5% dextrose solutions at both the minimum and maximum concentrations normally administered. Sodium heparin premixed infusion solutions in 5% dextrose and 0-45% sodium chloride were used as-is. Tirofiban HCl solutions were combined 1:1 (simulated Y-site administration) with the dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride solutions in separate glass containers and polyvinylchloride Y-site infusion lines. Samples were held for 4 h at room temperature under ambient fluorescent light and were assayed for changes in drug content, degradation, pH, appearance and turbidity. Activity of sodium heparin solutions was measured using an aPTT coagulation assay. All mixtures remained clear and colourless with no visual indication of instability, i.e. precipitation. Clarity of solutions was confirmed by turbidometric analysis. There was no significant loss of drug, increase in known degradates, or appearance of unknown drug-related peaks as determined by HPLC. The activity of heparin in heparin-containing solutions remained unchanged. The pH of all test-solutions remained constant. Tirofiban HCl injection 0.05 mg/ml can be co-infused by Y-site administration with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride injection solutions.

Brain Drug Delivery System Bearing Dopamine Hydrochloride for Effective Management of Parkinsonism

Dopamine hydrochloride bearing positively charged small liposomes was prepared by sonicating the multilamellar vesicles. These vesicles were characterized for their physical attributes (shape, size, charge, drug entrapment efficiency, and drug leakage). The drug release kinetics from the liposomes were also studied and found to be Fickian-type diffusion. In vivo performance of the drug-entrapped liposomes was assessed by periodic measurement of drug- (chlorpromazine) induced catatonia in Sprague-Dowley rats. These results were compared with the plain dopamine HCl and levodopa preparations as well with the marketed formulation of levodopa containing carbidopa (Syndopa®). These studies revealed that the dopamine can be effectively delivered to the brain by incorporating it into liposomes, and its degradation in circulation can also be protected. The results of liposomal formulation were found to be superior compared to plain levodopa as well as Syndopa.

Left atrial plication and mitral valve replacement for giant left atrium accompanying mitral lesion.

Between January 1982 and November 1992, 38 patients received simultaneous mitral valve replacement (MVR) and left atrial plication (LAP) because of giant left atrium accompanying mitral lesion. Their ages ranged from 33 to 70 years, and the mitral lesion was caused by rheumatic heart disease in all patients. MVR was performed with a St. Jude Medical prosthesis for all patients and the left atrial wall was plicated with running 3-0 Nespolene to reduce the width to 3 to 5 cm. Respiration requiring mechanical ventilation more than 48 hours after operation occurred in four patients (10.5%) and postoperative low cardiac output requiring a high dose of dopamine HCl or intraaortic balloon pumping in nine patients (23.7%). The left atrial diameter measured by echocardiogram was a mean of 7.3 +/- 1.0 cm before operation and 5.8 +/- 1.0 cm postoperatively. The cardiothoracic ratio on the chest roentgenogram registered a preoperative mean of 73.3% +/- 9.8% and was 65.7% +/- 8.4% after operation. The pre- and postoperative values were significantly different (p < 0.01). The postoperative exercise level was a mean of 5.3 metabolic units for 24 patients and the postoperative New York Heart Association functional classification indicated Class I or II for 37 patients with no evidence of left atrial thrombus except in the case of one early death. LAP with MVR for patients with giant left atrium due to mitral lesion appeared to result in improvement in respiratory and circulatory functions.

Arterial lesions in dopamine-infused rats

Dopamine is administered by intravenous infusion to maintain renal blood flow in patients with shock and congestive heart failure. This effect is probably due to dopamine receptors present in the renal vasculature. Dopamine also has agonist activity at α-adrenergic receptors which can evoke vasoconstriction. Alpha-adrenergic agonists produce medial necrosis in various arterial beds of the rat, including those in which dopamine exerts a vasodilator effect. To determine the effects on these arteries, we administered dopamine to rats by intravenous infusion and examined their gastric and renal arteries by transmission and scanning electron microscopy. Sprague Dawley rats were infused via tail vein with 20 μg/kg/min of dopamine HCl. For transmission EM (TEM), rats infused with dopamine for 1, 4 or 24 hours were perfused with 1% phosphate-buffered glutaraldehyde, post-fixed in 1% OsO4, stained en bloc with uranyl magnesium acetate, dehydrated and embedded in epoxy.

Pituitary function during the sexual maturation of the male rat: inhibition of prolactin secretion by exogenous dopamine.

Experiments were designed to determine if the responsiveness of the anterior pituitary to the prolactin (Prl) inhibiting effects of dopamine were altered during the sexual maturation of the male rat. Initial experiments established that bolus injection of dopamine HCl into cannulated (left carotid) rats pretreated with alpha-methyl-p -tyrosine (MPT) resulted in an appropriate reduction of serum Prl and that the MPT treatment did not significantly alter testosterone or luteinizing hormone (LH). Immature (25-30 days), pubertal (50-55 days), and young adult (75-80 days) rats were studied. One hour after MPT administration a blood sample was collected, followed by administration via the cannula of 2.5, 10, 40 or 160 micrograms dopamine/100 g BW or the 5% glucose vehicle. Additional blood samples were collected 15, 30, 45 and 60 min after dopamine. MPT administration resulted in a significant increase in serum Prl compared to saline-treated controls at all ages; however, the absolute value of these increases varied significantly with age. Subsequent data were calculated in terms of the decrement in serum Prl versus Time O. In immature rats the 160-micrograms dose of dopamine resulted in a significant inhibition of Prl at 15 and 30 min when compared to glucose-treated controls. In pubertal animals, 40 micrograms dopamine was effective in inhibiting Prl at both 15 and 30 min. In young adult rats, 10 micrograms dopamine was effective at 15 and 30 min; 160 micrograms lowered Prl through 45 min. These data suggest that the responsiveness of the pituitary to the Prl inhibiting effects of dopamine increases during the sexual maturation of the male rat.

1586 EFFECTS OF DOPAMINE ON CEREBRAL BLOOD FLOW (CBF) AND OXYGEN METABOLISM (CMRO2) IN DOGS UNDER THE INFLUENCE OF E COLI ENDOTOXIN (ET)

In normocapnic dogs ET causes a decreased CBF, an increased CMRO2 and decreased cardiac output (CO) and mean aortic pressure (MAP). With a defective blood-brain barrier during endotoxemia a direct influence of monoamines on the cerebral metabolism is possible. Dopamine (DA), a neurotransmittor, was used to test this hypothesis. In four dogs ET 1.0-1.5 mg/kg was injected over five minutes. CO and MAP were followed. CBF was measured using a radioactive gas elimination method (Xenon133). CMRO2 was calculated from CBF and the arteriovenous oxygen difference. Venous blood was sampled from the superior sagittal sinus. During the established shock phase dopamine HCl 10μg/kg min was infused. Effects after ET and ET+DA are compared. The same dose of DA without ET causes an increased CBF without affecting CMRO2. These results indicate a direct effect of DA on cerebral metabolism. The effects of ET can thus be influenced by treatments that normally would not affect the brain metabolism.