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Biomedical subjects

T Reisine

Publications and source records attributed to T Reisine.

At least 127 records · Page 7Linked to original sources
PubMed1985

Pertussis toxin blocks somatostatin inhibition of calcium mobilization and reduces the affinity of somatostatin receptors for agonists.

Both forskolin, the activator of adenylate cyclase, and 8-bromocyclic (cAMP) increase cytosolic calcium levels (measured using Quin 2) and adrenocorticotropin (ACTH) release from a tumor cell line of the mouse anterior pituitary (AtT-20/D16-16). Somatostatin (SRIF) blocks the ACTH release response to each secretagogue but only inhibits forskolin-stimulated calcium mobilization suggesting that SRIF prevents the formation of cAMP rather than blocking the ability of cAMP to raise intracellular calcium concentrations. SRIF itself lowers intracellular calcium levels. The ACTH release response but not the rise in cytosolic calcium levels induced by the membrane-depolarizing agent K+, is blocked by SRIF, indicating that SRIF can interfere with some intracellular event, other than calcium mobilization or cAMP formation, to reduce ACTH secretion. Pertussis toxin uncouples SRIF receptors from adenylate cyclase by catalyzing the ADP-ribosylation of an inhibitory guanine nucleotide binding protein (Ni) in AtT-20 cell membranes. Pretreatment of AtT-20 cells with pertussis toxin abolishes the inhibition by SRIF of the ACTH release response and of the rise in cytosolic calcium induced by forskolin. In addition, the ability of SRIF to inhibit basal calcium levels is prevented by pertussis toxin treatment. Pertussis toxin treatment also reduced the ability of SRIF to inhibit K+-evoked ACTH release. SRIF receptor binding studies using the ligand 125I-CGP-23996 revealed that pertussis toxin treatment greatly diminished the affinity of the SRIF receptor for SRIF and its structural analogs. These results indicate that, in addition to coupling SRIF receptors to adenylate cyclase, Ni is also involved in the lowering by SRIF of resting calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1984

Forskolin stimulates adenylate cyclase activity, cyclic AMP accumulation, and adrenocorticotropin secretion from mouse anterior pituitary tumor cells.

The effects of forskolin, an adenylate cyclase activator, were investigated on adrenocorticotropin (ACTH) secretion from AtT-20/ D16 -16 mouse pituitary tumor cells. Forskolin increased adenylate cyclase activity in these cells in the absence of added guanyl nucleotide, an effect blocked by somatostatin. Cyclic AMP synthesis and ACTH secretion increased in a concentration-dependent manner, not only in the clonal cells, but in primary cultures of rat anterior pituitary as well. Somatostatin inhibited cyclic AMP synthesis and ACTH secretion in response to forskolin. When forskolin was coapplied with corticotropin releasing factor, cyclic AMP synthesis was potentiated and ACTH secretion additive. The calcium channel blocker, nifedipine, inhibited forskolin, and 8-bromocyclic AMP stimulated ACTH secretion. These data suggest that ACTH secretion may be regulated at the molecular level by changes in cyclic AMP formation, which in turn regulate a calcium gating mechanism.

Adenylyl Cyclases↗
PubMed1984

Adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase activity in rodent pituitary tissue: possible role in cAMP-dependent hormone secretion.

A cAMP-dependent protein kinase occurs in the intermediate lobe of the rat pituitary gland and the ACTH-secreting tumor AtT-20/D16-16 derived from the mouse pituitary gland. Exposure of either tissue to drugs increasing cAMP production and hormone release (forskolin, cholera toxin, or isoproterenol in the case of the intermediate lobe; forskolin or isoproterenol in the case of the AtT-20 cells) increases the cAMP-dependent protein kinase activity of a tissue homogenate in the absence, but not in the presence, of added cAMP. The potencies of these drugs to induce changes in the protein kinase activity ratio (i.e. enzyme activity in the absence of cAMP to enzyme activity in the presence of 3 microM cAMP) are comparable with their potencies as stimulants of hormone secretion. In either tissue, A23187, a calcium ionophore that stimulates hormone release but not cAMP production, does not change the protein kinase activity ratio. In the case of the AtT-20 cells, dexamethasone blocks the release of ACTH simulated by either isoproterenol or forskolin, but does not alter the enhancement of protein kinase activity induced by these drugs. Conversely, dexamethasone does not block the A23187-stimulated release of ACTH. The data suggest that cAMP modulates (but does not trigger) hormone secretion from the rodent pituitary gland by a mechanism involving activation of the cAMP-dependent protein kinase. Several possible sites for this modulatory effect of cAMP are discussed.

Adrenocorticotropic Hormone↗
PubMed1984

Somatostatin desensitization: loss of the ability of somatostatin to inhibit cyclic AMP accumulation and adrenocorticotropin hormone release.

Addition of somatostatin (SRIF) inhibits corticotropin-releasing factor- and forskolin-stimulated cyclic AMP accumulation and adrenocorticotropin hormone secretion from mouse anterior pituitary tumor cells (AtT-20/D16-16). However, prior exposure of these cells to SRIF reduced the potency of SRIF to inhibit both corticotropin-releasing factor- and forskolin-stimulated cyclic AMP accumulation and adrenocorticotropin hormone release. This SRIF desensitization is time- and concentration-dependent and reversible. Cross-desensitization to SRIF analogs also occurred whereas SRIF pretreatment did not affect the inhibition by SRIF of 8-bromo-cyclic AMP-stimulated adrenocorticotropin hormone release or did it affect basal cyclic AMP levels, protein content or phosphodiesterase activity. These data indicate that SRIF can regulate the sensitivity of its own receptor and that SRIF desensitization may involve either a down-regulation of SRIF receptors or an uncoupling of these inhibitory receptors from adenylate cyclase.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Desensitization of corticotropin-releasing factor receptors.

Pretreatment of rat anterior pituitary cells with corticotropin releasing factor (CRF) rapidly and markedly reduced the ability of CRF to restimulate cyclic AMP formation and adrenocorticotropic hormone (ACTH) release. The effect was dependent on the length of time of pretreatment as well as the concentration of CRF. Neither basal nor intracellular immunoreactive ACTH levels nor basal cyclic AMP content were affected. CRF's stimulatory action on cyclic AMP formation and ACTH release recovered within one hour following CRF pretreatment. Forskolin, a compound that directly activates adenylate cyclase also releases ACTH from these cells. Pretreatment with CRF did not alter forskolin-stimulated cyclic AMP accumulation or ACTH secretion. Furthermore, CRF pretreatment did not change epinephrine's ability to increase the release of ACTH. These results indicate that CRF can regulate the responsiveness of its own receptor.

Adrenocorticotropic Hormone↗
PubMed1983

Desensitization of beta 2-adrenergic receptors and adrenocorticotropin release.

Pre-exposure of mouse anterior pituitary tumor cells (A+T-20/D16-16) to (-) isoproterenol reduces the ability of this beta-adrenergic agonist to restimulate cyclic AMP synthesis or adrenocorticotropin hormone (ACTH) release from these cells. This beta-adrenergic receptor desensitization is time and dose-dependent, recoverable and specific for beta-receptors. Longer pretreatment times are required to decrease beta-receptor density than to induce receptor desensitization. This initial beta-receptor refractoriness involves an uncoupling of the receptor from adenylate cyclase since (-) isoproterenol treatment does not alter forskolin-activated cyclic AMP formation or ACTH release. In addition to diminishing beta-receptor responsiveness, (-) isoproterenol treatment induces a prolonged elevation of basal ACTH release. This finding indicates that the intracellular events leading to ACTH secretion may also be altered during the desensitization process.

Adrenocorticotropic Hormone↗
PubMed1983

Prolonged somatostatin pretreatment desensitizes somatostatin's inhibition of receptor-mediated release of adrenocorticotropin hormone and sensitizes adenylate cyclase.

Addition of somatostatin-14 (SRIF) inhibits corticotropin releasing factor (CRF) and forskolin-stimulated cyclic AMP formation and ACTH release from tumor cells of the mouse anterior pituitary (AtT-20/D16-16). After long-term pretreatment of these cells with SRIF, the ability of SRIF to inhibit CRF and forskolin-stimulated cyclic AMP accumulation or ACTH secretion is markedly reduced. SRIF pretreatment also increases the formation of cyclic AMP in response to forskolin. This increase is delayed in onset, slow to recover, and blocked by the protein synthesis inhibitor, cycloheximide. SRIF pretreatment did not affect basal cyclic AMP and cyclic GMP levels or phosphodiesterase activity. It is proposed that prolonged treatment of AtT-20 cells with SRIF desensitizes SRIF receptors and induces a compensatory sensitization of adenylate cyclase through a process requiring protein synthesis.

Adenylyl Cyclases↗
PubMed1983

Desensitization of beta adrenergic receptors linked to adrenocorticotropin secretion.

Stimulation of beta adrenergic receptors on AtT-20 cells increases intracellular cyclic AMP levels and adrenocorticotropin hormone (ACTH) release. Pretreatment of these cells with catecholamines reduces the ability of (-)-isoproterenol to stimulate both cyclic AMP formation and ACTH secretion. This beta receptor desensitization is time- and dose-dependent and is reversible. Various beta adrenergic agonists can induce this desensitization with a rank order of potency of salmefamol greater than or equal to (-)-isoproterenol greater than or equal to epinephrine greater than or equal to norepinephrine greater than or equal to (+)-isoproterenol. (+/-)-Propranolol but not practolol can block the (-)-isoproterenol-induced beta receptor desensitization. Long-term treatment of AtT-20 cells with (-)-isoproterenol reduces the density of beta receptors but does not affect the affinity of these sites for [3H]dihydroalprenolol. In addition to desensitizing beta receptors, (-)-isoproterenol pretreatment enhances basal ACTH secretion. This effect was dose-dependent and blocked by (+/-)-propranolol. Forskolin-stimulated cyclic AMP formation and ACTH secretion was not altered by (-)-isoproterenol treatment indicating that the desensitization of beta receptors on AtT-20 cells is the result of receptor-adenylate cyclase uncoupling. No cross-desensitization of corticotropin releasing factor or vasoactive intestinal peptide receptors occurred as (-)-isoproterenol treatment did not alter the effect of these peptides on cyclic AMP synthesis or ACTH secretion.

Adrenergic beta-Agonists↗
PubMed1982

Application of L-glutamic acid and substance P to the substantia nigra modulates in vivo [3H]serotonin release in the basal ganglia of the cat.

L-Glutamic acid or substance P were applied to the caudate nucleus (CN) or substantia nigra (SN) and their effects on local, spontaneous, in vivo [3H]serotonin ([3H]5-HT) release as well as [3H]5-HT release in the contralateral CN and SN were studied using cats implanted with push-pull cannulae. L-Glutamic acid (5 x 10(-5) M), when applied to the CN or SN inhibited the local release of [3H]5-HT but did not affect release in the contralateral CN and SN. In the SN, the L-glutamic acid effect was blocked by L-glutamic acid diethylester. Substance P (10(-7) M) applied to the SN induced an increase in [3H]5-HT release that was delayed in onset. Furthermore, [3H]5-HT release was elevated in the contralateral CN immediately upon the application of substance P to the SN. These results suggest that L-glutamic acid and substance P may control 5-HT transmission in the basal ganglia.

Animals↗
PubMed1982

Sensory stimuli differentially affect in vivo nigral and striatal [3H]serotonin release in the cat.

The effect of auditory, visual and peripheral nerve stimulation on in vivo [3H]serotonin release in both caudate nuclei and substantiae nigrae was studied in either awake 'encéphale isolé' or halothane-anesthetized cats. Release of endogenously synthesized [3H]serotonin was estimated in each brain structure, using push--pull cannulae, continuously superfused with [3H]tryptophan. Bilateral and simultaneous application of click noises and light flashes to awake 'encéphale isolé' cats enhanced [3H]serotonin release in both substantiae nigrae but was without effect on striatal [3H]serotonin release. Unilateral, low intensity electrical stimulation of the forepaw of halothane-anesthetized cats diminished [3H]serotonin release in both caudate nuclei and the ipsilateral substantia nigra. No effect was observed in the contralateral substantia nigra. In contrast, high-intensity electrical stimulation of one forepaw increased [3H]serotonin release in the ipsilateral substantia nigra but was without significant effect on release in the other brain areas examined. The results are discussed in light of previously known anatomical data concerning serotoninergic pathways and electrophysiological evidence of the effect of sensory stimuli on serotoninergic neurons. Our findings suggest that serotonin neurons may serve an important function in the integration of sensory information.

Acoustic Stimulation↗
PubMed1982

Loss of rat cerebral cortical opiate receptors following chronic desimipramine treatment.

The characteristics of central opiate and beta-adrenergic receptors were studied after giving the tricyclic antidepressant desimipramine (DMI) to rats. Administration of DMI for 1 or 7 days did not alter cortical opiate or beta-adrenergic receptors. However, after 21 days of treatment there was a significant subsensitivity of both these receptors in the cortex. A specific loss of receptor sites for opiate binding was detected with no change in affinity. After a similar time of treatment, opiate receptors in the corpus striatum and hippocampus were the same as the controls. The data suggest that change in cortical opiate receptors may be important in the mechanism of action of antidepressants.

Animals↗
PubMed1982

Striatal dopamine release in vitro: a beta-adrenoceptor-regulated response not mediated through cyclic AMP.

The effects of (-)isoproterenol (10(-6) M), dibutyryl cyclic AMP (10(-3) M), and the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) (10(-4) M) on in vitro [3H]dopamine ([3H]DA) efflux and synthesis were studied in rat striatal slices continuously superfused with [3H]tyrosine. The beta-adrenoceptor agonist (-)isoproterenol induced an immediate and significant facilitation of [3H]DA efflux but did not alter [3H]DA synthesis as measured by [3H]H2O formation. In contrast, both dibutyryl cyclic AMP and IBMX enhanced [3H]DA synthesis as well as efflux. The presence of IBMX in the superfusing medium did not potentiate the augmentation of [3H]DA efflux caused by (-)isoproterenol. Additionally, the blockade of [3H]DA synthesis by alpha-methyl-p-tyrosine (10(-4) M) completely prevented the action of dibutyryl cyclic AMP on [3H]DA efflux. However, under similar conditions, (-)isoproterenol was still able to increase [3H]DA efflux. The results suggest that (-)isoproterenol can modify striatal DA release through a mechanism not involving cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1981

In vivo evidence for GABAergic control of serotonin release in the cat substantia nigra.

Push-pull cannulae were used for estimating the release of endogenously synthesized [3H]serotonin in both substantia nigra and caudate nuclei of halothane-anaesthetized cats. The unilateral nigral application of GABA (10-5 M) reduced the local release of [3H]serotonin picrotoxin induced an opposite effect. Both treatments failed to modify [3H]serotonin release in the caudate nuclei or in the contralateral substantia nigra. These results suggest that GABAergic neurons innervating the substantia nigra may regulate nigral serotonin transmission. The possibility that such a regulation could be presynaptic (direct or through other nigral neurotransmitters) or related to a change in the activity of the nigro-raphe projection is discussed.

Animals↗