Effects of the cilioexcitatory neurohumors dopamine and 5-hydroxytryptamine on cyclic AMP levels in the gill of the mussel Mytilus edulis.

Cyclic 3′, 5′-adenosine monophosphate (cAMP) has been identified in the ciliated gill epithelium of the marine mussel $\text{Mytilus}$$\text{edulis}$. In concentrations which stimulate the rate of particle transport by frontal gill cilia, DA and 5HT stimulate levels of cAMP within the gill. The stimulation occurs in as early as 15 sec and is graded from 10^?6M to 10^?4M. DA plus 5HT is not additive at maximal effective concentrations of both amines. ACH does not mimic the DA or 5HT stimulation of cAMP. Theophylline alone has a weak effect on cAMP levels; however, the effect of theophylline is potentiated in the presence of DA or 5HT. Dibutyryl cAMP produces a gradual stimulation in the rate of particle transport. It is suggested that the dopaminergic and serotonergic excitatory control of particle transport by frontal gill cilia of $\text{Mytilus}$$\text{edulis}$ is mediated through a cAMP second messenger system.     

The stimulating effect of 3′,5′-(cyclic)adenosine monophosphate and lipolytic hormones on 3-O-methylglucose transport and 45Ca2+ release in adipocytes and skeletal muscle of the rat

(1) In order to assess the possible role of 3′,5′-(cyclic)adenosine monophosphate (cAMP) in the control of glucose transport, the effect of the nucleotide or agents known to increase its intracellular concentration on sugar transport or ⁴⁵Ca²⁺ washout were characterized in epididymal fat pads, free fat cells and soleus muscles of the rat. (2) When added to the incubation medium, cAMP (0.1–2.0 mM) stimulated $\text{3-O-[}{}^{14}\text{C}\text{]}\text{methylglucose}$ washout from fat pads. This effect was abolished by cytochalasin B, and additive to that induced by submaximal (10–25 μU/ml), but not by supramaximal (10 mU/ml) concentrations of insulin. (3) cAMP (2 mM) stimulated the conversion of [U-¹⁴C]glucose into CO₂ and triacylglycerols. This effect was additive to that of insulin (100 μU/ml). (4) ACTH, glucagon, adrenaline, noradrenaline and salbutamol, which are all known to increase the cAMP content of adipose tissue, stimulated the washout of $\text{3-O-[}{}^{14}\text{C}\text{]}\text{methylglucose}$ and ⁴⁵Ca²⁺ from preloaded fat pads. The fractional losses of the two isotopes were significantly correlated ($\text{P < 0.001}$, $\text{r = 0.73}$). (5) In free fat cells, adrenaline (10^?6 M) and salbutamol (10^?5 M) stimulated the uptake of $\text{3-O-[}{}^{14}\text{C}\text{]}\text{methylglucose}$, and salbutamol (10^?5 M) did not interfere with the stimulating effect of insulin (25 μU/ml) on sugar uptake. (6) In rat soleus muscles, adrenaline and salbutamol produced a dose-dependent stimulation of the washout of $\text{3-O-[}{}^{14}\text{C}\text{]}\text{methylglucose}$ and ⁴⁵Ca²⁺. The effect of adrenaline on sugar efflux was abolished by propranolol. (7) It is concluded that the activation of the glucose transport system by insulin is unlikely to be mediated by a drop in the cellular concentration of cAMP. An increase in cAMP brought about by β-adrenoceptor agonists or lipolytic hormones may induce a mobilization of calcium ions from cellular pools into the cytoplasm, which in turn leads to the activation of the glucose transport system demonstrated in the present as well as in several earlier studies.     

1-substituted tetrahydroisoquinoline analogs: beta adrenoceptor blocking agents in the isolated perfused rabbit heart.

The 1-benzyl and 1-methyl congeners of trimetoquinol were tested for antagonism of receptors which mediate inotropy and chronotropy in the isolated perfused rabbit heart. 1-Benzyltrimetoquinol was found to be a blocker of resting, isoproterenol- and dobutamine-stimulated inotropy at concentrations (10^?7?10^?5M) which did not significantly affect chronotropy ( > 10^?5M). 1-Methyltrimetoquinol was found to be a partial agonist in the resting myocardium, weakly blocking inotropy and chronotropy at doses of 10^?7?10^?5M. At a concentration of 10^?4M, 1-methyltrimetoquinol was an agonist of both chronotropy and inotropy. These stimulatory properties appear to be direct (not affected by prior reserpinization) and antagonized by propranolol. In the isoproterenol-stimulated heart, 1-methyltrimetoquinol was a specific negative inotropic agent at doses (10^?7?10^?5M) above which agonist properties were manifest. At 10^?4M, 1-methyltrimetoquinol acted synergistically with isoproterenol to produce positive inotropy and chronotropy significantly greater than that of isoproterenol alone. Currently, it is believed that the receptors which mediate inotropy and chronotropy are $\text{beta}$ adrenergic in nature. Thus, it would appear that 1-benzyltrimetoquinol is a specific antagonist of those $\text{beta}$-receptors which mediate inotropy, while 1-methyltrimetoquinol is a partial agonist of both inotropic and chronotropic $\text{beta}$-receptors. Further, the response to these compounds does not appear to be proportionate in various regions of the myocardium.     

Characteristics of synaptosomal tyrosine uptake in various brain regions: Effect of other amino acids

Tyrosine uptake by rat synaptosomes was maximal after 5–10 min of incubation and at 30°C; uptake was inhibited by dinitrophenol (10^?4 M) or ATP (10^?3 M) and increased by reducing sodium concentrations or increasing calcium or potassium. The best model for uptake is a two-carrier system, in which one carrier shows high-affinity uptake and the other may be diffusional. Both uptake mechanisms are more concentrated in catecholamine-rich brain areas, and are inhibited $\text{in vitro}$ by other large, neutral amino acids. At physiologic amino acid brain concentrations, each system probably carries about half of the tyrosine into the nerve terminal.     

Malaria enhances cyclic AMP production by immature erythrocytes in vitro.

Infection with a chloroquine-susceptible line of $\text{Plasmodium}$$\text{berghei}$ NYU-2 enhanced the production of cyclic AMP in response to isoproterenol only in immature mouse erythrocytes, which possess a functional hormone-receptor-adenylate cyclase complex. With 10^?7 M isoproterenol the increases in cyclic AMP concentrations (picomoles per 10⁸ erythrocytes) were 19 for a preparation of mature erythrocytes, 81 for a preparation enriched with immature erythrocytes, 25 for a preparation of infected mature erythrocytes, and 900 for a preparation enriched with infected immature erythrocytes. Beta-adrenergic receptor blockade with propranolol prevented this response to isoproterenol but had no effect on the stimulation produced by prostaglandin E₁. These findings indicate that the malaria parasite enhances the responsiveness of a fundamental regulatory system that is intrinsic to immature erythrocytes.     

Adrenocorticotropin regulates angiotensin II receptors in bovine adrenal cells in vitro

The role of ACTH-(1–24) on angiotensin II receptors has been studied in bovine adrenal glomerulosa cells in primary culture. Angiotensin II receptors were measured in cells pretreated or not by ACTH-(1–24) on day 4 of culture. ACTH-(1–24) decreased angiotensin II binding sites in a time and a dose-dependent manner. After 24 hours of treatment the minimal effective dose of ACTH-(1–24) was 10^?11M and the maximal effect was obtained with 10^?8M. Moreover, ACTH-(1–24) 10^?8M decreased significantly angiotensin II receptors after 6 hours of treatment. Scatchard plot analysis showed that ACTH-(1–24) treatment did not modify the affinity of angiotensin II receptors (Ka = 0.42 and 0.44 × 10⁹M^?1 in control and treated cells respectively) but reduced by about half the number of angiotensin II sites per cell. Like ACTH-(1–24), 8-Bromo-cAMP, forskolin and cholera toxin decreased angiotensin II receptors. Factors such as prolactin, somatostatin, ACTH-(11–24) and dopamine which are bound to adrenal membranes without increasing cAMP production had no effect. In conclusion, these studies $\text{in vitro}$ demonstrate for the first time that ACTH decreases angiotensin II receptors by a direct mechanism acting on glomerulosa cells, and they also suggest that this effect could be mediated by cAMP.     

Parallel activation of cyclic AMP phosphodiesterase and cyclic AMP-dependent protein kinase in two human gut adenocarcinoma cells (HT 29 and HRT 18) in culture,by vasoactive intestinal peptide (VIP) and other effectors activating the cyclic AMP system

Vasoactive intestinal peptide (VIP), secretin, catecholamines and prostaglandin E₁ (PGE₁) in the presence of a cyclic nucleotide phosphodiesterase inhibitor stimulate the accumulation of cyclic AMP in two colorectal carcinoma cell lines (HT 29 and HRT 18) with subsequent activation of the cyclic AMP-dependent protein kinases. In HT 29 cells incubated without phosphodiesterase inhibitor, 10^?9 M VIP promotes a rapid and specific activation of the low $\text{K}{}_{\mathrm{<mtext>m</mtext>}}$ cyclic AMP phosphodiesterase (1.7-fold); at 25°C the effect is maintained for more than 15 min, while at 37°C the activity returns to basal value within 15 min. As shown by dose-response studies, VIP is by far the most effective inducer ($\text{K}{}_{\mathrm{<mtext>a</mtext>}}\text{= 4 · 10}{}^{\mathrm{?10}}\text{M}$) of the cyclic AMP phosphodiesterase activity; partial activation of the enzyme is obtained by 3 · 10^?7 M secretin, 10^?5 M isoproterenol and 10^?5 M PGE₁; PGE₂ and epinephrine are without effect. In HRT 18 cells VIP is less active ($\text{K}{}_{\mathrm{<mtext>a</mtext>}}\text{= 2 · 10}{}^{\mathrm{?9}}\text{M}$) whereas 10^?6 M PGE₁, 10^?6 M PGE₂ and 10^?5 M epinephrine are potent inducers of the phosphodiesterase activity. The positive cell response to dibutyryl-cyclic AMP further indicates that cyclic AMP is a mediator in the phosphodiesterase activation process. The incubation kinetics and dose response effects of the various agonists on the cyclic AMP-dependent protein kinase activity determined for both cell types in the same conditions show a striking similarity to those of phosphodiesterase. Thus coordinate regulation of both enzymes by cyclic AMP was observed in all incubation conditions.     

Inhibition by dexamethasone of the in vitro transport of 3-O-methylglucose into rat thymocytes

Reduced glucose transport across the plasma membrane and reduced phosphorylation may both be responsible for the early inhibitory effect of physiological concentrations of glucocorticoids on glucose uptake by rat thymocytes.The early inhibitory effects of glucocorticoids (5 · 10^?7 M dexamethasone) on glucose consumption and ¹⁴CO₂ formation from d-[U-¹⁴C]glucose were reproduced.The total uptake curve of 4.8 μM $\text{3-O-[}{}^{14}\text{C}\text{]}\text{methyl-}\text{d}\text{-glucose}$ was biexponential with $\text{t}\text{1}\text{2}$ of 1.1 min and 36 min, respectively, the rapid part comprising about 50% of the equilibrated intracellular water space. The latency of the effect of 5 · 10^?7 M dexamethasone on $\text{3-O-[}{}^{14}\text{C}\text{]}\text{methyl-}\text{d}\text{-glucose}$ uptake ranged from 15 to 100 min and the inhibition varied from 15 to 55% independently of the lag period. The effect of 3-O-methylglucose concentration on the initial uptake by steroid-responsive cell preparations was tested after 45 min of preincubation with or without 5 · 10^?7 M dexamethasone. In 12 experiments dexamethasone reduced V from 1.36 ± 0.16 mmol · min^?1 · l^?1 cell water to 0.81 ± 0.10 mmol · min^?1 · l^?1 cell water with insignificant change of K_m (6.0 mM versus 5.9 mM). Dexamethasone had similar effect after 90 or 120 min.The variabilities of control cell transport capacity, the lag period and the magnitude of the dexamethasone effect could not be accounted for by changes in pH, effects of cell density, concentrations of albumin, ethanol, nucleosides, pyruvate or correlated to age and sex of the rats. In conclusion the inhibition of glucocorticoids on glucose consumption by thymocytes appears to be an inhibited plasma membrane transport capacity.     

Greatly extended viability of rat brain storage vesicles in an intracellular medium based upon a non-permeant polyanion

The MgATP-stimulated accumulation of (-)-³H-nor- epinephrine (NE) by rat brain neuronal storage vesicles has been characterized in a new medium based upon polyacrylic acid (avg. MW 5,000). The medium allows careful regulation of K⁺ concentration (140 mM), has a large buffer capacity, and is non-permeant to membranes. Light scattering measurements have confirmed the osmotic stability of vesicles suspended in this medium. Vesicular accumulation of (-)-³ H-NE (Km 1 × 10^?6 M) in this system (37°) was examined under saturating (10^?5 M) and non-saturating (2 × 10^?7 M) concentrations of NE. At 10^?5 M NE, uptake saturated at 5 min and remained stable for periods up to one hour, with maximal uptake levels (pmol/mg protein) of 15.7±0.30 (37°), 3.0±0.49 (0°), 4.4±0.22 (reserpine pretreated $\text{in}$$\text{vivo}$) and 6.0±0.79 (without MgATP). At 2×10^?7 M NE uptake was biphasic with maximal uptake levels (pmol/mg protein) of 4.04±0.14 (37°), 0.19±0.01 (0°), 0.95±0.01 (reserpine) and 0.83±0.08 (without MgATP). Vesicle preparations refrigerated in this medium for 24 hrs displayed properties quite similar to those measured acutely (NE = 2.2x10^?7 M).     

Selective antilipolytic effect of bacitracin in the isolated fat cell

Bacitracin, an antibiotic which decreases extracellular degradation, has been used to study peptide hormone degradation $\text{in}\text{vitro}$. The biologic effectiveness of these hormones in the presence of bacitracin has received minimal attention. This study demonstrates inhibition of lipolysis induced by both epinephrine and glucagon in the isolated fat cell (IFC). IFC from epididymal tissue were incubated with 0.5 μM epinephrine and increasing concentrations of bacitracin. Lipolysis was inhibited in a dose-dependent fashion, with a concentration of 5.7 × 10^?4$\text{M}$ bacitracin suppressing lipolysis 50%. Increasing the concentration of epinephrine in the presence of a constant dose of bacitracin overcame the antilipolytic effect. Bacitracin did not increase oxidation of glucose-U-C¹⁴ over basal. In the perifusion system, acute exposure to 5.7 × 10^?4$\text{M}$ bacitracin plus 5 × 10^?9$\text{M}$ glucagon suppressed lipolysis below unstimulated basal levels. Constant bacitracin perifusion produced no change in basal lipolysis but blunted the response to glucagon. ¹²⁵I-glucagon degradation was decreased in the presence of bacitracin. Additional studies with dibutyryl cyclic AMP demonstrated that the antilipolytic effect of bacitracin is exerted at a step beyon the second messenger. Bacitracin exerts a direct antilipolytic effect in isolated fat cells without stimulating glucose uptake and may afford a means of studying antilipolysis in the absence of other insulin-like effects.     

Nature of progesterone action on amino acid uptake by isolated full-grown oocyte of Xenopus laevis

l-leucine uptake into full-grown oocytes of Xenopus laevis is a saturable process which is Na⁺ dependent and presumably coupled to Na⁺ gradient. Our results indicate that progesterone (10^?6 M) blocks abruptly, around the germinal vesicle breakdown, the saturable transport of l-leucine. $\text{p-}\text{Chloromercuribenzoate}$ (10^?4 M) induces maturation and after a short lag of time strongly inhibits l-leucine uptake. Cycloheximide prevents progesterone-induced maturation and permeability changes.     

Effect on an antagonistic analog of gonadotropin releasing hormone upon ovarian granulosa cell function.

We have recently demonstrated that gonadotropin releasing hormone (GnRH) acts directly on ovarian granulosa cells to inhibit the follicle stimulating hormone (FSH)-induced increase in granulosa cell steroidogenesis $\text{in}$$\text{vitro}$. A GnRH antagonist, [D-pGlu¹, D-Phe², D-Trp^3,6] GnRH (A), which is known to antagonize GnRH-stimulated gonadotropin release by cultured pituitary cells, was tested in the granulosa cell system. GnRH (10^?8M) inhibited estrogen and progesterone production by FSH-treated granulosa cells $\text{in}$$\text{vitro}$, whereas the antagonist A (10^?6M) did not affect FSH stimulation of steroidogenesis. Antagonist A, when added together with GnRH and FSH, blocked the GnRH inhibition of FSH-induced steroidogenesis. Estrogen and progesterone production by granulosa cells was increased by 50% at a molar ratio (IDR₅₀) of $\text{20}\text{1}\text{and}\text{12}\text{1}$ ([antagonist]/[GnRH]), respectively. At 10^?6M, antagonist A completely prevented the GnRH (10^?8M) inhibition. A similar effect of antagonist A was seen in FSH-induced increase of luteinizing hormone (LH) receptor content. FSH treatment for 2 days $\text{in}$$\text{vitro}$ induced an 8-fold increase in LH receptor content in cultured granulosa cells; concomitant treatment with 10^?8M GnRH completely inhibited the FSH effect. Antagonist A (10^?6M), by itself, had no effect on the FSH action. However, when added together with FSH and GnRH, antagonist A completely abolished the inhibitory effect of GnRH. These results demonstrate that the direct inhibitory effect of GnRH on granulosa cell function can be prevented by a GnRH antagonist and that the GnRH action at the ovarian level may require stringent stereospecific interactions of these peptides with putative GnRH recognition sites.     

Testosterone induces a rapid stimulation of endocytosis,amino acid and hexose transport in mouse kidney cortex

Testosterone induced a rapid (<1 min) stimulation of endocytosis, amino acid and hexose transport, measured by the temperature-sensitive uptake of HRP, ¹⁴C-AIB and ³H-DG, in mouse kidney cortex slices. The hormonal increment in uptake persisted for at least 60–120 min, showed time-, energy-, and Na⁺-dependence, and varied with substrate and testosterone concentration. Testosterone was maximally effective at 10^?8 to 10^?7 M. Peroxidase histochemistry indicated that the hormonal increase in HRP uptake is restricted to proximal tubules. Testosterone was more effective than DHT, whereas cyproterone acetate, androsterone and dexamethasone had little or no stimulating effect on this uptake. Kidney slices from androgen-insensitive $\text{tfm}\text{Y}$ mice did not respond to testosterone. The rapid increase in endocytosis, amino acid and hexose transport may represent a direct, receptor-mediated response of the surface membrane of target cells to testosterone.     

Catecholamine-stimulation of Cl− secretion in MDCK cell epithelium

Cultured epithelial monolayers of MDCK cells grown upon Millipore filter supports and mounted in Ussing chambers for transport studies respond to addition of $\text{5 · 10}{}^{\mathrm{?7}}\text{M}$ adrenalin from only the basal bathing solution by an increased short-circuit current, due both to an increased transmonolayer potential difference (basal solution electropositive) and an increased transmonolayer conductance. Measurement of tracer Na⁺, K⁺ and Cl^? fluxes demonstrate that the adrenalin-stimulated short-circuit current results primarily from basal to apical net Cl^? secretion. Half-maximal stimulation of the short-circuit current was observed at ($\text{3.1 ± 0.3) · 10}{}^{\mathrm{?8}}\text{M adrenalin}$; the order of potency of adrenergic agonists for short-circuit current stimulation was $\text{isoprenalin}\text{>}\text{adrenalin}\text{>}\text{noradrenalin}$, consistent with adrenalin action being mediated by a β-adrenergic receptor. The adrenalin-stimulated short-circuit current was sensitive to inhibition (75%) by basal additions of furosemide ($\text{1 · 10}{}^{\mathrm{?4}}\text{M}$); phloretin inhibition (54%, 57%) was observed from both epithelial surfaces. Amiloride (10^?4 M) and 4-acetamido-4-isothiocyanostilbene-2, 2′-disulphonic acid (SITS) (10 μM) were ineffective as inhibitors of the adrenalin response. The increased short-circuit current was sensitive to replacement of medium Na⁺ by choline (87%) and Tris (93%). Li⁺ was a partially effective substitute cation for Na⁺ · NO₃^?, and isethionate were ineffective substitutes for Cl^? whereas Br^? was partially effective. Partial replacement of medium Na⁺ by choline gave an upward-curving non-saturable dependence of the adrenalin-stimulated short-circuit current upon [Na]; partial replacement of Cl^? by NO₃^? in contrast gave a saturable increase with a $\text{K}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ of approx. 65 mM Cl^?.     

Beta-(2-furyl)-acryloyl phosphate hydrolase activity in insect cell surface membranes

In primary cultures of adult rat hepatocytes, dexamethasone (10^?5M) induced tyrosine aminotransferase (TAT) 24 h after its addition. Glucagon (10^?7M) alone had no effect, but strongly enhanced the induction by dexamethasone. Glucagon could be replaced by butyryl cyclic-AMP (10^?4M), which caused about 20-fold increase in activity. In contrast to many previous reports that insulin induced TAT activity $\text{in}\text{vivo}$ and $\text{in}\text{vitro}$, it inhibited the inductions of TAT by dexamethasone and dexamethasone plus glucagon 24 h after its addition. However, insulin significantly induced TAT activity in the early pahse, 4 h after its addition. Dose-response curves of the effect of insulin on TAT activity showed reverse relations to activity in early and late phase. These results show that TAT activity is regulated by insulin in a two phase fashion.     

Evidence for an electrogenic ATPase in microsomal vesicles from pea internodes

The transmembrane electropotential of microsomal vesicles from pea internode segments, monitored by equilibrium distribution of the permeant anion SCN^?, is strongly hyperpolarized when ATP is present in the incubation medium.The stimulation of SCN^? uptake by ATP is rather specific with respect to the other nucleoside di- and triphosphates tested: ADP, GTP, CTP and UTP. ATP-stimulated SCN^? uptake is strongly inhibited by ATPase inhibitors such as $\text{p-}\text{chloromercuribenzenesulphonate}$ and $\text{N,N}{}^{\mathrm{\prime }}\text{-}\text{dicyclohexylcarbodiimide}$ and by 2.5% toluene/ethanol (1 : 4, v/v), the latter being a treatment which makes the vesicles permeable. On the contrary, oligomycin is almost ineffective in influencing ATP-induced SCN^? uptake. The proton conductor carbonyl cyanide $\text{p-}\text{trifluoromethoxyphenylhydrazone}$ strongly inhibits ATP-stimulated SCN^? uptake. The effect of ATP on SCN^? uptake depends on the pH of the medium, the maximum being reached at about pH 7.0.These data support the view that microsomal fractions from pea internodes contain membrane vesicles endowed with a membrane-bound ATPase coupling ATP hydrolysis to electrogenic transport of ions, probably H⁺.     

Catecholamine-mediated constrictor effects of aldosterone on vascular smooth muscle

The possibility that the corticosteroid hormone, aldosterone, might possess direct vasoconstrictor properties was examined in the isolated central ear artery of the New Zealand white rabbit. Aldosterone alone produced only minimal contractile effects in the arterial segments; but following pretreatment of the tissue with desipramine (10^?7M), a blocker of neuronal uptake of norepinephrine, aldosterone concentrations of 10^?6M, 10^?5M, and 10^?4M produced stepwise contractile responses of 0.16 ± 0.03 (SE)g, 0.48 ± .04g, and 1.31 ± 0.06g. The possible involvement of norepinephrine in this action of aldosterone was tested in a series of tissues stored for 2 days at 2°C in Krebsbicarbonate medium so as to deplete endogenous catecholamine stores. Treatment with desipramine followed by aldosterone (10^?4M) now produced an average contraction of only 0.1 ± 0.06g; but if the labile neuronal tissue stores of norepinephrine in these tissues were then replenished by exposure to norepinephrine 10^?7M, contractions of 1.2 ± 0.3g now occurred when desipramine and aldosterone were added. To examine whether aldosterone's action might be due to blockade of extraneuronal norepinephrine uptake (uptake-2), ³H-norepinephrine was added to ear artery tissues exposed to desipramine with or without aldosterone: a significant (P<0.005) decrease of 25% in ³H-norepinephrine uptake occurred in the tissues treated with aldosterone. In further studies, the contractile effects of aldosterone could be prevented by pretreatment with prazosin (10^?7M) or phentolamine (10^?7M); if added after the aldosterone, each of these alpha-blockers completely reversed the contractile responses. Although the physiological relevance of these findings is yet to be fully defined, these studies indicate that the $\text{in}$$\text{vitro}$ contractile effects of aldosterone are dependent upon its inhibition of extraneuronal uptake of endogenous norepinephrine; it is likely that the resulting increase in extracellular norepinephrine concentration then produces vasoconstriction by stimulation of post-synaptic alpha-adrenergic receptors.     

Actions of morphine on prostate gland fructose metabolism

Varying doses of morphine sulfate (10, 20 or 40 mg/kg daily × 10) were observed to suppress metabolic activities in the mouse prostate gland. Prostate gland fructose, an index of androgenic activity, was significantly reduced by these dose regimes of morphine (P < 0.01). Injections of morphine sulfate (20 mg/kg daily × 10) led to an inhibitition in the $\text{in vitro}$ synthesis of both fructose^?14C and sorbitol^?14C from glucose^?14C by the prostate gland, part of which may have been due to decreased uptake of glucose by the gland. The $\text{in vitro}$ assimilation of 2-deoxyglucose^?14C by the prostate was also reduced by morphine treatment. The $\text{in vitro}$ actions of morphine (2 × 10^?3M) on the metabolism of radioactive glucose by the mouse prostate gland likewise revealed a significant reduction in the formation of sorbitol^?14C, but no decrease in fructose^?14C formation. These results indicate that both the $\text{in vitro}$ and $\text{in vivo}$ actions of morphine can inhibit fructose metabolism in the prostate gland.