Neurotransmitter receptor activation triggers p27(Kip1 )and p21(CIP1) accumulation and G1 cell cycle arrest in oligodendrocyte progenitors

We examined the pathways that link neurotransmitter receptor activation and cell cycle arrest in oligodendrocyte progenitors. We had previously demonstrated that glutamate receptor activation inhibits oligodendrocyte progenitor proliferation and lineage progression. Here, using purified oligodendrocyte progenitors and cerebellar slice cultures, we show that norepinephrine and the beta-adrenergic receptor agonist isoproterenol also inhibited the proliferation, but in contrast to glutamate, isoproterenol stimulated progenitor lineage progression, as determined by O4 and O1 antibody staining. This antiproliferative effect was specifically attributable to a beta-adrenoceptor-mediated increase in cyclic adenosine monophosphate, since analogs of this cyclic nucleotide mimicked the effects of isoproterenol on oligodendrocyte progenitor proliferation, while alpha-adrenoceptor agonists were ineffective. Despite the opposite effects on lineage progression, both isoproterenol and the glutamate receptor agonist kainate caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1)and p21(CIP1), and G1 arrest. Studies with oligodendrocyte progenitor cells from INK4a-/- mice indicated that the G1 cyclin kinase inhibitor p16(INK4a) as well as p19(ARF)were not required for agonist-stimulated proliferation arrest. Our results demonstrate that beta-adrenergic and glutamatergic receptor activation inhibit oligodendrocyte progenitor proliferation through a mechanism that may involve p27(Kip1) and p21(CIP1); but while neurotransmitter-induced accumulation of p27(Kip1) is associated with cell cycle arrest, it does not by itself promote oligodendrocyte progenitor differentiation.     

Noradrenergic potentiation of cerebellar Purkinje cell responses to GABA: cyclic AMP as intracellular intermediary

Norepinephrine and the beta-adrenergic receptor agonist, isoproterenol, have been shown to potentiate the amplitude of GABAA receptor-mediated whole-cell current responses in Purkinje cells acutely dissociated from the rat cerebellum. However, the steps leading from the activation of beta-adrenergic receptors to the modulation of GABAA receptor remain to be delineated. This study tested the hypothesis that a sequelae of intracellular intermediaries involving the cyclic AMP second messenger system serves as the subcellular link to promote this heteroreceptor interaction. Exposure to cholera toxin, but not to pertussis toxin, increased the amplitude of GABA-activated current responses in acutely dissociated Purkinje cells. Intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) also resulted in a time- and dose-dependent augmentation of the response to GABA. while guanosine 5'-O-(2-thiodiphosphate) blocked the norepinephrine-mediated facilitation. A positive modulation of the current response to GABA was observed following intracellular delivery of cyclic AMP or the catalytic subunit of the cyclic AMP-dependent protein kinase. Furthermore, the norepinephrine-induced potentiation of the GABA-activated current response was prevented in the presence of the Rp isomer of cyclic AMP, the regulatory subunit of cyclic AMP-dependent protein kinase and an inhibitor of cyclic AMP-dependent protein kinase. These findings led to the formulation of a working model in which activation of the beta-adrenergic receptor triggers a Gs-protein-mediated transduction cascade in cerebellar Purkinje cells which activates adenylate cyclase, resulting in a rise in intracellular levels of cyclic AMP, increased phosphorylating activity by cyclic AMP-dependent protein kinase and, ultimately, a potentiation of GABAA receptor function.     

Does Ca2+ channel blockade modulate the antidepressant-induced changes in mechanisms of adrenergic transduction?

We investigated how the L-type calcium channel blockade (CCB) with nifedipine affects the cyclic AMP responses to noradrenaline or isoproterenol in cerebral cortical slices from rats receiving antidepressant treatments that induce (electroconvulsive shock, imipramine) or do not induce (amitriptyline) beta-downregulation. To assess the role of protein kinase C (PKC) in receptor crosstalk under CCB conditions, the cyclic AMP responses were tested also in the presence of a PKC activator, TPA. CCB alone induced no changes, but modulated the action of those antidepressants that down regulate the beta-adrenergic system. Chronic ECS and imipramine treatments were differently affected. ECS, under conditions of CCB, down regulated the response to isoproterenol in the presence of TPA, while imipramine ceased to block the TPA-potentiation of cyclic AMP responses. Thus, CCB affects the processes related to the antidepressant-induced changes on the crosstalk between alpha1- and beta-adrenergic receptors, depending on the specific properties of the antidepressant.     

The S5-S6 linker of repeat I is a critical determinant of L-type Ca2+ channel conductance

The alpha1-subunits of the skeletal and cardiac L-type calcium channels (L-channels) contain nearly identical pore regions (P-regions) in each of the four internal homology repeats. In spite of this high conservation of the P-regions, native skeletal L-channels exhibit a unitary conductance that is only about half that of native cardiac L-channels. To identify structural determinants of this difference in L-channel conductance, we have characterized unitary activity in cell-attached patches of dysgenic myotubes expressing skeletal, cardiac, and chimeric L-channel alpha1-subunits. Our results demonstrate that the S5-S6 linker of repeat I (IS5-IS6 linker) is a critical determinant of the difference in skeletal and cardiac unitary conductance. The unitary conductances attributable to the wild-type skeletal (CAC6; approximately 14 pS) and cardiac (CARD1; approximately 25 pS) alpha1-subunits expressed in dysgenic myotubes are identical to those observed in native tissues. Chimeric alpha1-subunits containing skeletal sequence for the first internal repeat and all of the putative intracellular loops (SkC15), the IS5-IS6 linker and the intracellular loops (SkC51), or only the IS5-IS6 linker (SkC49) each exhibit a low, skeletal-like unitary conductance (< or = 17 pS). Constructs in which the IS5-IS6 linker is of cardiac origin (CARD1 and CSk9) display cardiac-like conductance (approximately 25 pS). Unitary conductance and the rate of channel activation are apparently independent processes, since both SkC51 and SkC49 exhibit low, skeletal-like conductance and rapid, cardiac-like rates of ensemble activation. These results demonstrate that the IS5-IS6 linker strongly influences the single channel conductance of L-channels in a manner that is independent from the rate of channel activation.     

Beta-adrenoceptor-linked protein kinase A (PKA) activity in human fibroblasts from normal subjects and from patients with major depression

Human fibroblasts from normal subjects and from patients with major depression are cultured and their beta-adrenoreceptor-cyclic AMP-protein kinase A (PKA) system characterized. The results indicate that the beta-adrenoreceptor-mediated activation of PKA in the 900 g supernatant fraction of human fibroblasts is mediated via beta-adrenoreceptors. The activation of PKA by isoproterenol is very rapid with maximal stimulation occurring at 5 seconds. The time course of PKA activation by isoproterenol in fibroblasts from patients with major depression is identical to that in fibroblasts from normal subjects but the magnitude of activation is significantly reduced in fibroblasts from patients with major depression. Dose-response curves on cyclic AMP mediated activation of PKA confirmed the previously reported reduction in activation of PKA in patients with major depression but demonstrated that this reduction occurs without a change in the EC50 values of cyclic AMP (approximately 20 nmol/L). The blunted beta-adrenoceptor-linked PKA responses in patients with major depression occur without a change in the expression of the PKA catalytic subunit C alpha. The studies suggest that the beta-adrenoceptor-coupled adenylate cyclase PKA system in human fibroblasts may represent a valid model to explore possible abnormalities in the fine tuning of the beta-adrenergic transduction cascade in patients with affective disorders.     

Metabotropic glutamate receptor agonists potentiate cyclic AMP formation induced by forskolin or beta-adrenergic receptor activation in cerebral cortical astrocytes in culture

The metabotropic glutamate receptor (mGluR) agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) potentiated the accumulation of cyclic AMP induced by either beta-adrenergic receptor stimulation (isoproterenol) or direct activation of adenylyl cyclase (AC) with forskolin in rat cerebral cortical astrocytes grown in a defined medium. In contrast, ACPD inhibits the cyclic AMP response in astrocytes cultured in a serum-containing medium. Pharmacological characterization indicated that a group I mGluR, of which only mGluR5 is detectable in these cells, is involved in the potentiation of cyclic AMP accumulation. Potentiation was elicited by mGluR I agonists [e.g., (R,S)-3,5-dihydroxyphenylglycine (DHPG)], but not by mGluR II or III agonists; it was pertussis toxin resistant and abolished by procedures suppressing mGluR5 function (phorbol ester pretreatment or DHPG-induced receptor down-regulation). Nevertheless, it appears that products generated through the mGluR5 transduction pathway, such as elevated [Ca2+]i or activated protein kinase C (PKC), are not involved in the potentiation as it was not influenced by either the intracellular calcium chelator BAPTA-AM or the PKC inhibitor Ro 31-8220. An inhibitor of phospholipase C, U-73122, markedly attenuated mGluR5-activated phosphoinositide hydrolysis but did not significantly affect the DHPG potentiation of the cyclic AMP response. A mechanism is proposed in which the potentiating effect on AC could be mediated by free betagamma complex that is liberated after the agonist-bound mGluR5 interacts with its coupled G protein.     

Differences in tryptophan binding to hepatic nuclei of NZBWF1 and Swiss mice: insight into mechanism of tryptophan''s effects

Catecholamine receptors of multiple classes have been shown to influence pineal melatonin synthesis in a species-specific manner. In these experiments, the effects of catecholamine receptor agonists on circadian melatonin rhythms of zebrafish (Danio rerio) pineal in vitro were examined. Cyclic application of adrenergic receptor agonists (norepinephrine, phenylephrine, clonidine, and isoproterenol) had no effect on zebrafish pineal melatonin release, nor on the circadian oscillator that regulates melatonin rhythms. Pineal melatonin release was partially suppressed by quinpirole, a D2 dopamine receptor agonist, but cyclic application of quinpirole did not reset the pineal circadian oscillator. Pineal melatonin release was unaffected by either dopamine or SKF38393, a D1 receptor agonist, suggesting that the effects of quinpirole were not mediated by dopamine receptors. The regulatory mechanisms underlying pineal melatonin rhythms appear to differ among teleosts.     

Endogenous norepinephrine regulates tumor necrosis factor-alpha production from macrophages in vitro

Evidence for the extraneuronal accumulation of norepinephrine has been demonstrated to occur in macrophage (M phi), yet the physiologic role of this system remains undefined. We have assessed the response of murine peritoneal M phi to adrenergic antagonists. We have also defined a physiologic role of a M phi-associated pool of the nonspecific adrenergic agonist norepinephrine. We investigated the constitutive involvement of alpha-adrenergic and beta-adrenergic receptors in LPS-induced TNF-alpha production. CFA-elicited M phis were incubated with LPS (1 microgram/ml) in the presence or absence of adrenergic agonists and/or antagonists. Although stimulation of alpha-adrenergic receptors increased TNF production and gene expression, beta-adrenergic receptors decreased it. Interestingly, when adrenergic antagonists along with LPS alone were added to M phi, they generated the response opposite to that produced by their suitable agonist, suggesting a role for endogenous norepinephrine in M phi. Thus, although alpha 2-adrenergic antagonists attenuated TNF production, beta-adrenergic antagonists augmented TNF expression in a concentration-dependent manner. Norepinephrine and epinephrine were found in M phi as determined by HPLC and LPS stimulation induced a significant decrease in their content. M phis were also incubated with LPS or medium only, washed, and then challenged 12 h later with LPS. When given a second LPS stimulation, M phis were found to have an increased response to alpha 2-adrenergic agonists and decreased response to alpha 2-adrenergic antagonists. Therefore, M phi-associated norepinephrine appears to regulate LPS-induced TNF production in an autocrine fashion.     

Modulation of the stress-induced synthesis of hsp27 and alpha B-crystallin by cyclic AMP in C6 rat glioma cells

The possible participation of cyclic AMP in the stress-induced synthesis of two small stress proteins, hsp27 and alpha B-crystallin, in C6 rat glioma cells was examined by specific immunoassays, western blot analysis, and northern blot analysis. When C6 cells were exposed to arsenite (50-100 microM for 1 h) or heat (42 degrees C for 30 min), expression of hsp27 and alpha B-crystallin was stimulated, with levels of the two proteins reaching a maximum after 10-16 h of culture. Induction of hsp27 was markedly enhanced when cells were exposed to arsenite in the presence of isoproterenol (20 microM) or epinephrine (20 microM) but not in the presence of phenylephrine. The stimulatory effects of isoproterenol and epinephrine were blocked completely by propranolol, an antagonist of beta-adrenergic receptors. Cholera toxin (2 micrograms/ml), forskolin (20 microM), and dibutyryl cyclic AMP (2.5 mM), all of which are known to increase intracellular levels of cyclic AMP, also stimulated the arsenite- or heat-induced accumulation of hsp27. Treatment of cells with each of these modulators alone did not result in the induction of hsp27. The level of hsp70 in C6 cells, as estimated by western blot analysis, was also enhanced by arsenite or heat stress. However, induction of hsp70 by stress was barely stimulated by isoproterenol. By contrast, induction of alpha B-crystallin by heat or arsenite stress was suppressed when isoproterenol, cholera toxin, forskolin, or dibutyryl cyclic AMP was present during the stress period. Northern blot analysis of the expression of mRNAs for hsp70, hsp27, and alpha B-crystallin showed that the modulation of the stress-induced accumulation of the three hsps by the various agents was regulated at the level of the corresponding mRNA. These results indicate that stress responses of hsp70, hsp27, and alpha B-crystallin in C6 rat glioma cells are regulated differently and, moreover, that when the level of cyclic AMP increases in cells, the response to stress of hsp27 is stimulated but that of alpha B-crystallin is suppressed.     

Response and level of beta-adrenergic, vasoactive intestinal peptide, and PACAP receptors during the circadian cycle

PURPOSE: To determine whether a nocturnal increase of ciliary process beta-adrenergic receptor responsiveness can explain the observation that timolol decreased the aqueous flow rate and intraocular pressure (IOP) during the night but not during the day in rabbits. METHODS: Rabbits were housed in alternating 12-hour periods of light and dark. In vitro stimulation of tissue cyclic adenosine monophosphate (cAMP) levels by isoproterenol (ISO), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), or a soluble derivative of forskolin (sFSK) was measured in ciliary processes harvested at mid-light phase and early and late dark phase. Inhibition of ISO and VIP stimulation of ciliary process cAMP by an alpha 2-adrenergic agonist and maximal binding of [125I]I-pindolol, [125I]I-VIP, and [125I]I-PACAP in ciliary process membranes were measured at the same three times. RESULTS: Although there may have been a nocturnal increase in the sensitivity of ciliary process cAMP levels to stimulation by ISO, this was not observed consistently, VIP, but not PACAP, stimulation increased at night, but there was no change in the response to sFSK. Inhibition by apraclonidine of elevated ciliary process cAMP levels was constant at all three times. Ligand-binding studies showed little change in ciliary process beta-adrenergic, VIP-, or PACAP-receptor levels at the three times. CONCLUSIONS: There is no convincing evidence for a nocturnal increase in beta-adrenergic receptor sensitivity in rabbit ciliary processes that could explain the difference between day and night effects of timolol on aqueous flow and IOP.     

Activation of alpha 2-adrenoceptors causes inhibition of calcium channels but does not modulate inwardly-rectifying K+ channels in caudal raphe neurons

Many neurotransmitter receptors that interact with pertussis toxin-sensitive G proteins, including the alpha 2-adrenergic receptor, can modulate both voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels. Serotonergic neurons of the medulla oblongata (nucleus raphe obscurus and nucleus raphe pallidus), which provide a major projection to sympathetic and motor output systems, receive a catecholaminergic input and express alpha 2-adrenergic receptors. Therefore, we tested the effects of norepinephrine on voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels in neonatal raphe neurons using whole-cell recording in a brainstem slice preparation. Calcium channel currents were inhibited by norepinephrine in the majority of raphe neurons tested (88%) and in all identified tryptophan hydroxylase-immunoreactive (i.e. serotonergic) neurons. When tested in the same neurons, the magnitude of calcium current inhibition by norepinephrine (approximately 25%) was less than that induced by 5-hydroxytryptamine (approximately 50%). The norepinephrine-induced calcium current inhibition was mediated by alpha 2-adrenergic receptors; it was mimicked by UK 14304, an alpha 2-adrenergic receptor agonist and blocked by idazoxan, an alpha 2-adrenergic receptor antagonist, but not affected by prazosin or propanolol (alpha 1 and beta adrenergic antagonists, respectively). Calcium current inhibition by norepinephrine was essentially eliminated following application of omega-Conotoxin GVIA and omega-Agatoxin IVA, indicating that norepinephrine modulated N- and P/Q-type calcium channels predominantly. Calcium current inhibition by norepinephrine was voltage-dependent and mediated by pertussis toxin-sensitive G proteins. Thus, as expected, alpha 2-adrenergic receptor activation inhibited N- and P/Q-type calcium currents in medullary raphe neurons via pertussis toxin-sensitive G proteins. In parallel experiments, however, we found that norepinephrine had no effect on G protein-coupled inwardly-rectifying K+ channels in any raphe neurons tested, despite the robust activation of those channels in the same neurons by 5-hydroxytryptamine. Together, these data indicate that alpha 2-adrenergic receptors can modulate N- and P/Q-type calcium channels in caudal medullary raphe neurons but do not couple to the G protein-coupled inwardly-rectifying K+ channels which are also present in those cells. This is in contrast to the effect of 5-hydroxytryptamine1A receptor activation in caudal raphe neurons, and indicates a degree of specificity in the signalling by different pertussis toxin-sensitive G protein-coupled receptors to voltage-dependent calcium channels and G protein-coupled inwardly-rectifying K+ channels even within the same cell system.     

Involvement of methionine in the synthesis of certain membrane-associated nucleotide sugars by human amnion (WISH) cells

OBJECTIVE: To investigate the influence of age on the venodilator effect of isoproterenol, a beta-adrenoceptor agonist, and amrinone, a selective phosphodiesterase (PDE) III inhibitor, in human subjects. METHODS: In eight young and eight elderly male subjects, the drugs were infused into a dorsal hand vein preconstricted with phenylephrine and its diameter was measured using a linear variable differential transformer. RESULTS: The maximum venodilation (Emax) induced by isoproterenol was significantly smaller and the infusion rate of isoproterenol required to induce 50% of maximum venodilation (ED50) was significantly larger in the elderly than in the young subjects [Emax: 29.8 vs 95.1%, ED50: 97.3 vs 51.6 ng.min-1]. A significant age-related change in Emax or ED50 was not observed for amrinone (Emax: 95.8 vs 100.8%, ED50: 40.1 vs 31.6 micrograms.min-1). CONCLUSION: The data show that the venodilator effect of amrinone is not influenced by age. As amrinone increases cyclic AMP by inhibition of PDE III, it is suggested that the action of cyclic AMP is not altered by age. The decreased effect of isoproterenol might be caused by reduced production of cyclic AMP in elderly subjects.     

Characterization of postsynaptic alpha-1 and alpha-2 adrenoceptors in the feline saphenous and femoral veins [corrected

Experiments were designed to characterize the effects mediated by alpha-1 and alpha-2 adrenoceptors in saphenous and femoral veins of the cat. Ring segments of saphenous and femoral veins were mounted for isometric tension recording in modified Krebs-bicarbonate solution, gassed with 95% O2-5% CO2 and maintained at 37 degrees C. Norepinephrine (a mixed alpha 1 and alpha 2 agonist), phenylephrine (a preferential alpha 1 agonist) and clonidine (a preferential alpha 2 agonist) caused dose (concentration)-dependent contractions in saphenous and femoral veins. The maximal contractions produced by clonidine were significantly less than those produced by norepinephrine or phenylephrine in both veins. However, threshold dose and EC50 values indicated that clonidine was more potent than norepinephrine and phenylephrine. Contractile responses to these agonists were attenuated when the veins were pretreated with alpha 1-or alpha 2-adrenoceptor antagonists, prazosin and yohimbine, respectively. The contractile responses to norepinephrine and tyramine were inhibited to a greater extent by yohimbine than by prazosin in both saphenous and femoral veins, suggesting that norepinephrine released from perivascular nerve terminals activates preferentially postsynaptic alpha 2-adrenoceptors. Further examination of alpha-adrenoceptor subtypes was achieved by comparing pA2 values of prazosin and yohimbine from Arunlakshana and Schild plots. Chronic sympathetic denervation by removing lumbar sympathetic chain significantly reduced the contractile responses evoked by tyramine. Denervation did not significantly affect the concentration-response curve to phenylephrine but significantly augmented the contractile responses evoked by clonidine in both veins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction between alpha- and beta-adrenergic receptor agonists modulating the slow Ca(2+)-activated K+ current IAHP in hippocampal neurons

Noradrenaline inhibits the Ca(2+)-activated K+ current IAHP, which underlies the slow afterhyperpolarization and spike frequency adaptation in hippocampal and neocortical neurons. The resulting increase in excitability probably contributes to the state control of the forebrain during arousal and attention. The modulation of IAHP by noradrenaline has previously been shown to be mediated by beta 1 receptors, cyclic AMP and protein kinase A, but not by alpha receptors. We have now tested the possibility that alpha receptors also contribute to IAHP modulation through interaction with beta receptors, by the use of whole-cell recordings in CA1 pyramidal cells of rat hippocampal slices. The alpha-receptor agonist 6-fluoro-noradrenaline strongly potentiated the effect of isoproterenol on IAHP. The synergistic effect of 6-fluoro-noradrenaline and isoproterenol was blocked by the beta-receptor antagonist timolol, but the receptor type mediating the effect of 6-fluoro-noradrenaline could not be unequivocally identified by using alpha-receptor antagonists. The effect of high concentrations of noradrenaline on IAHP was only partly blocked by the beta-receptor antagonist timolol, and was further reduced by blocking alpha receptors, again suggesting a contribution from alpha receptors. In contrast, the effect of low concentrations of noradrenaline seemed to be potentiated by the alpha-receptor antagonist phentolamine in 57% of the cells, suggesting concentration-dependent antagonistic interaction between alpha and beta receptors. Further tests indicated that the cross-talk between 6-fluoro-noradrenaline and isoproterenol occurs upstream from cyclic AMP production, and that protein kinase A serves as a final common path for the modulation of IAHP by noradrenaline, and by the combination of 6-fluoro-noradrenaline and isoproterenol.     

Exogenous and endogenous catecholamines inhibit the production of macrophage inflammatory protein (MIP) 1 alpha via a beta adrenoceptor mediated mechanism

Noradrenaline (NA) and adrenaline (Ad) are modulators of cytokine production. Here we investigated the role of these neurotransmitters in the regulation of macrophage inflammatory protein (MIP)-1alpha expression. Pretreatment of RAW 264.7 macrophages with NA or Ad decreased, in a concentration-dependent manner (1 nM-100 microM), MIP-1alpha release induced by bacterial lipopolysaccharide (LPS 10 ng ml(-1) LPS). The effect of NA was reversed by the selective beta-adrenoceptor antagonist propranolol (10 microM), but not by the alpha-adrenoceptor antagonist phentolamine (10 microM). In the concentration range of 10 nM-10 microM, isoproterenol, a beta-adrenoceptor agonist, but not phenylephrine (a selective alpha1-adrenoceptor agonist) or UK-14304 (a selective alpha2-adrenoceptor agonist) mimicked the inhibitory effects of catecholamines on MIP-1alpha production. Increases in intracellular cyclic adenosine monophosphate, elicited either by the selective type IV phosphodiesterase inhibitor rolipram (0.1 - 10 microM), or by prostaglandin E2, (10 nM-10 microM) decreased MIP-1alpha release, suggesting that increased cyclic AMP may contribute to the suppression of MIP-1alpha release by beta-adrenoceptor stimulation. Northern blot analysis demonstrated that NA (100 nM-10 microM), Ad, isoproterenol, as well as rolipram (100 nM-10 microM) decreased LPS-induced MIP-1alpha mRNA accumulation. NA and Ad (1-100 microM) also decreased MIP-1alpha production in thioglycollate-elicited murine peritoneal macrophages. Pretreatment of mice with either isoproterenol (10 mg kg(-1), i.p.) or rolipram (25 mg kg(-1), i.p.) decreased LPS-induced plasma levels of MIP-1alpha, while propranolol (10 mg kg(-1), i.p.) augmented the production of this chemokine, confirming the role of a beta-adrenoceptor mediated endogenous catecholamine action in the regulation of MIP-1alpha production in vivo. Thus, based on our data we conclude that catecholamines are important endogenous regulators of MIP-1alpha expression in inflammation.     

Studies on the hypocalcemic actions of salmon calcitonin and ultimobranchial gland extracts in the freshwater teleost Cyprinus carpio

The equatorial current of the frog lens was studied with microelectrodes and a vibrating probe. Norepinephrine, isoproterenol and terbutaline applied topically at the surface of the cornea as a 1% solution increased the equatorial current of the lens about 80%. This increase was blocked by timolol. Topical forskolin increased the equatorial current by over 80%. This effect of forskolin was not blocked by timolol. These substances did not affect the equatorial current of the lens when the lens was suspended in a frog Ringers solution. 8-Bromo cyclic AMP increased the equatorial current when it was applied topically but not when it was added directly to the medium bathing an isolated lens. The results suggest that beta-adrenergic agonists, applied topically to the cornea, increase the equatorial current of the lens by a mechanism that is mediated by cyclic AMP. The finding that 8-bromo cyclic AMP did not act directly on the lens suggests that a currently unknown substance or process is active at the level of the lens.