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T Reisine

Publications and source records attributed to T Reisine.

At least 91 records · Page 5Linked to original sources
PubMed1991

Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs.

Somatostatin receptor subtypes were labeled with the somatostatin analogs [125I]CGP 23996 and [125I]MK 678 and the distribution of these receptors in rat brain was investigated using quantitative autoradiographic techniques. [125I]CGP 23996 and [125I]MK 678 specifically label different populations of somatostatin receptors in rat brain. In a number of brain regions striking differences in the distribution of the somatostatin receptor subtypes labeled by each peptide were observed. High levels of binding sites for both [125I]CGP 23996 and [125I]MK 678 were present in the cerebral cortex, CA1 region and subiculum of the hippocampus. In contrast, high levels of [125I]MK 678 binding were found in the dentate gyrus of the hippocampus while few [125I]CGP 23996 binding sites were observed in this brain region. [125I]CGP 23996 binding was detected in the central region of the interpeduncular nucleus whereas the dorsal and lateral subnuclei of this brain area expressed mainly somatostatin receptors with high affinity for MK 678. The locus coeruleus and regions of the superior colliculus and hypothalamus selectively express [125I]MK 678-sensitive somatostatin receptors. Furthermore, limbic structures such as the lateral septum, the nucleus accumbens and ventromedial striatum had much higher levels of [125I]MK 678 binding sites than [125I]CGP 23996 binding sites. Differences in the expression of the somatostatin receptor subtypes were also detected in the substantia nigra. [125I]CGP 23996 binding was present in the pars reticulata but not the pars compacta whereas the reverse distribution for [125I]MK 678 binding sites was observed. The differential distribution of [125I]CGP 23996 and [125I]MK 678 binding sites in rat brain supports the hypothesis that these peptides selectively label different somatostatin receptor subtypes in the central nervous system.

Animals↗
PubMed1991

Subtypes of brain somatostatin receptors couple to multiple cellular effector systems.

To investigate whether somatostatin (SRIF) receptor subpopulations mediate different physiological actions of SRIF, we tested the effects of SRIF and the SRIF agonists MK 678 and CGP 23996 on different biological responses in rat neocortical neurons in culture. Neocortical cells in culture express SRIF receptors that can be labeled with 125I-MK 678 and 125I-CGP 23996. Pharmacological analysis of the binding sites indicates that the radioligands label SRIF receptor subtypes with distinct pharmacological characteristics. These receptor subpopulations are similar to those expressed in adult rat brain. SRIF, MK 678, and CGP 23996 are able to inhibit forskolin-stimulated adenylate cyclase activity in rat neocortical membranes by 25-30%. Furthermore, they inhibit a high voltage-activated Ca2+ current in rat neocortical neurons in culture by 25-35%. Both SRIF and MK 678 potentiate a delayed rectifier K+ current in rat neocortical neurons in culture by 25-30%. In contrast, high concentrations of CGP 23996 do not alter the K+ current. In cells that do not respond to CGP 23996, MK 678 increases the delayed rectifier K+ current. The findings of these studies indicate that rat neocortical neurons in culture express functionally distinct SRIF receptor subtypes that can be differentially activated by SRIF agonists.

Adenylyl Cyclases↗
PubMed1990

Pertussis toxin in the analysis of receptor mechanisms.

G proteins play a critical role in signal transduction across cell membranes. Information about the diversity of G protein structure and function has provided valuable insights into the nature of the complex actions exerted by hormones and neurotransmitters on different cells and biological systems. A common finding of the biophysical and biochemical studies described above is that G proteins have the potential to couple neurotransmitter or hormone receptors to multiple cellular effector systems. When this occurs in a cell, it may allow a particular hormone or transmitter to regulate a variety of different cellular events simultaneously. Furthermore, it has become clear that different receptors can couple to the same G protein. When this occurs in the same cell, it may provide the basis for the convergent regulation of cell activity by various hormones or neurotransmitters. Thus, G proteins greatly diversify the manner by which hormones and neurotransmitters can regulate cells. As more information is available on the mechanisms by which G proteins recognize and interact with receptors and effector systems, we may be able to better understand the specific events involved in signal transduction and the subtle processes by which hormones and neurotransmitters can control cell activity.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Biochemical properties of somatostatin receptors.

Somatostatin (SRIF) induces its biological actions by binding to and stimulating membrane-associated receptors. To investigate the molecular mechanisms by which SRIF induces its biological effects, we have characterized the biochemical properties of SRIF receptors. SRIF receptors can be solubilized in an active form with the detergent CHAPS and can be detected with the high-affinity SRIF analog [125I]MK 678. The pharmacological characteristics of solubilized SRIF receptors from brain are similar to the receptors in membranes, suggesting that the solubilized receptors retain their biological activity. Solubilized SRIF receptors appear to be tightly associated with GTP-binding proteins, since analogs of GTP can greatly reduce agonist labeling of the solubilized SRIF receptor. The solubilized SRIF receptor migrates as a mass of approximately 400 kd and is a glycoprotein since it can specifically interact with lectin columns. The solubilization of the SRIF receptor has allowed for its purification by affinity chromatography. The purified SRIF receptor migrates as a mass of 60 kd in denaturing gels. Using affinity chromatography, the receptor can be purified to near homogeneity. Present studies are directed toward sequencing and cloning cDNA encoding the SRIF receptor in order to further characterize its physical properties and expression.

Animals↗
PubMed1990

Electrophysiological effects of somatostatin-14 and somatostatin-28 on mammalian central nervous system neurons.

Somatostatin (SOM) exists in at least two active forms in the central nervous system (CNS): SOM-14 and SOM-28. These peptides have multiple actions on neurons in the CNS and these actions appear to be mediated by different receptors. Thus, SOM-14 can enhance voltage-dependent K currents, whereas SOM-28 inhibits these same currents, sometimes even in the same neurons. These effects are not mediated via cAMP, but do seem mediated by GTP-binding proteins. On the other hand, both forms of SOM inhibit a voltage-dependent Ca current, again via a GTP-binding protein. SOM can also interact with the GABA(A) receptor to modulate responses to this inhibitory transmitter. The physiological effects of SOM in an integrated circuit within the CNS will depend on the form of SOM released, the kinds and numbers of receptors present on the postsynaptic neurons, and the presence of other neurotransmitters.

Animals↗
PubMed1990

Somatostatin-14 and somatostatin-28 inhibit calcium currents in rat neocortical neurons.

The prosomatostatin-derived peptides, somatostatin-14 and somatostatin-28, are believed to function as neurotransmitters or neuromodulators in the cerebral cortex. To investigate the molecular mechanisms by which these peptides induce their physiological effects in the cerebral cortex, we have examined the effects of somatostatin-14 and somatostatin-28 on voltage-dependent Ca2+ currents in rat neocortical neurons in culture. Ca2+ currents were recorded using whole-cell patch-clamp techniques under conditions in which K+ and Na+ currents were blocked. Ca2+ currents were induced by depolarization from the holding potential of -80 mV. Somatostatin-14 (100 nM) and somatostatin-28 (100 nM) did not significantly affect low-voltage activated Ca2+ currents, but blocked high-voltage activated Ca2+ currents and slowed the activation of this current. The effects of both peptides were concentration-dependent and reversible. Furthermore, the effects of somatostatin-14 and somatostatin-28 on the high-voltage activated Ca2+ currents were not additive, suggesting that both peptides regulate this ionic current through similar cellular mechanisms. When patch pipettes used to record the Ca2+ currents contained 100 microM cAMP and 0.5 mM isobutylmethylxanthine, a phosphodiesterase inhibitor, somatostatin-14 and somatostatin-28 still inhibited Ca2+ currents, indicating that the effects of these peptides on the Ca2+ currents were cAMP-independent. Inclusion of the non-hydrolysable guanine triphosphate analogue, guanine triphos-somatostatin-14 or somatostatin-28, suggesting the involvement of guanine nucleotide binding proteins in the actions of the peptides on the Ca2+ currents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Expression of functional pituitary somatostatin receptors in Xenopus oocytes.

Functional somatostatin (SRIF, somatotropin release-inhibiting factor) receptors were expressed in Xenopus oocytes after injection of RNA isolated from the anterior pituitary tumor cell line AtT20. SRIF receptors were detected by measuring the ability of SRIF to inhibit cAMP formation stimulated by beta 2-adrenergic agonists in individual oocytes. beta 2-Adrenergic receptors (beta 2ARs) were expressed in oocytes by coinjecting RNA prepared by in vitro transcription of a beta 2AR cDNA clone with the pituitary cell RNA. Uninjected oocytes do not express detectable levels of either beta 2ARs or SRIF receptors. In oocytes coinjected with AtT20 and beta 2AR RNA, on the other hand, isoproterenol treatment led to a 2- to 3-fold increase in cAMP levels, whereas cotreatment with SRIF reduced this accumulation by 50-60%. The SRIF precursor somatostatin-28 and the cyclohexapeptide agonist MK678 also inhibited cAMP formation, whereas the biologically inactive N-terminal 14-amino acid fragment of somatostatin-28 was ineffective. The ability to detect changes in cAMP levels in individual oocytes may provide a simple procedure for the expression cloning of SRIF receptor cDNAs and other receptors functionally coupled to stimulation or inhibition of adenylate cyclase.

Animals↗
PubMed1990

Pancreatic beta-cell somatostatin receptors.

The characteristics of somatostatin (SRIF) receptors in rat pancreatic beta-cells were investigated using rat islets and the beta-cell line HIT-T15 (HIT). The biochemical properties of the SRIF receptors were examined with 125I-labeled des-Ala-1,Gly-2-desamino-Cys-3-[Tyr-11]- dicarba3,14-somatostatin (CGP 23996). 125I-CGP 23996 bound to SRIF receptors in HIT cells with high affinity and in a saturable manner. The binding of 125I-CGP 23996 to SRIF receptors was blocked by SRIF analogues with a rank order of potency of somatostatin 28 (SRIF-28) greater than D-Trp-8-somatostatin greater than somatostatin 14 (SRIF-14). To investigate the physical properties of the HIT cell SRIF receptor, the receptor was covalently labeled with 125I-CGP 23996 using photo-cross-linking techniques. 125I-CGP 23996 specifically labeled a protein of 55 kDa in HIT cell membranes. The size of the SRIF receptor in HIT cells is similar to the size of the SRIF receptor labeled with 125I-CGP 23996 in membranes of freshly isolated islets, suggesting that the physical properties of SRIF receptors in HIT cells and rat islet cells are similar. The binding studies suggest that beta-cells predominantly express a SRIF-28-preferring receptor. In freshly isolated islets, glucose- and arginine-stimulated insulin release was effectively blocked by SRIF-28 but not by SRIF-14. SRIF-14 did inhibit arginine-stimulated glucagon secretion from freshly isolated islets. The dissociation of the inhibitory effects of SRIF-28 and SRIF-14 on insulin and glucagon release from freshly isolated islets suggests that the two peptides act through different receptors in islets to regulate hormone secretion.

Animals↗
PubMed1990

Cellular mechanisms of somatostatin inhibition of calcium influx in the anterior pituitary cell line AtT-20.

The cellular mechanisms by which the hypothalamic peptide somatostatin (SRIF) inhibits Ca+(+) influx were investigated in the pituitary cell line AtT-20. Cytosolic Ca+(+) levels were measured using the fluorescent probe Quin 2. Calcium influx was stimulated by the Ca+(+) channel agonist Bay K 8644. Bay K 8644 increased Ca+(+) influx in a concentration-dependent manner and the stimulation of Ca+(+) influx was blocked by the Ca+(+) channel antagonists nifedipine and nitrendipine. SRIF analogs also blocked Bay K 8644-stimulated Ca+(+) influx. The rank order of potency of the analogs (SRIF-28 greater than D-Trp8-SRIF greater than SRIF) suggests that the effects of SRIF are mediated by SRIF-28 preferring receptors. Pretreatment of AtT-20 cells with pertussis toxin abolished SRIF's inhibition of Bay K 8644-evoked Ca+(+) influx suggesting that G proteins mediate the inhibitory effects of SRIF on Ca+(+) influx. The K+ channel antagonists tetraethylammonium, 4-aminopyridine and CsCl all stimulated Ca+(+) influx into AtT-20 cells. These agents did not alter Bay K 8644-evoked Ca+(+) influx or did they affect the ability of SRIF to inhibit Ca+(+) influx. Tetrodotoxin, the sodium channel blocker which inhibits action potential generation in AtT-20 cells, lowered basal Ca+(+) levels in AtT-20 cells but did not modify SRIF's inhibition of Bay K 8644-stimulated Ca+(+) influx. These findings suggest that SRIF receptors, linked directly to Ca+(+) channels via G proteins, may mediate SRIF's inhibition of Ca+(+) influx.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Solubilization of active somatostatin receptors from rat brain.

Rat brain somatostatin (SRIF) receptors were solubilized in an active form with the detergent 3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Solubilized SRIF receptors were detected with the stable SRIF analog 125I-MK 678. CHAPS solubilized approximately 30% of membrane-bound SRIF receptors. 125I-MK 678 binding to the solubilized SRIF receptors reached equilibrium by 90 min and dissociated from the receptor with a t1/2 of 60 min. The binding of 125I-MK 678 to the solubilized SRIF receptor was of high affinity and was selective. The characteristics of 125I-MK 678 binding to the solubilized and membrane-bound SRIF receptors were similar. The solubilized brain SRIF receptor specifically bound to a wheat germ agglutinin-Sepharose column, suggesting that it is a glycoprotein. Analysis of the solubilized SRIF receptor by gel exclusion chromatography on an AcA 34 Ultrogel column revealed that its molecular mass is approximately 400 kDa. This mass is probably representative of the receptor complexed with other proteins or molecules. Further characterization of the fractionated 400-kDa species by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting indicated that Gi and Go may be associated with the solubilized SRIF receptor. This is supported by the finding that guanosine-5'-O-(3-thio)triphosphate abolished 125I-MK 678 binding to the solubilized SRIF receptor. Antibodies directed against a synthetic peptide corresponding to a region of the C-terminal of Gia, which specifically immunoprecipitate Gia, immunoprecipitated over 24% of the solubilized SRIF receptor, suggesting that the receptor, in part, is coupled to Gi. These studies describe for the first time the characterization of the solubilized SRIF receptor in an active form. The ability to solubilize the SRIF receptor should allow for further characterization of its physical properties.

Animals↗
PubMed1990

Lack of cross-desensitization of somatostatin-14 and somatostatin-28 receptors coupled to potassium channels in rat neocortical neurons.

The effects of somatostatin-14 (SOM-14) and somatostatin-28 (SOM-28) on the delayed rectifier K+ current (IK) in rat neocortical neurons in culture were measured by using whole-cell patch clamp techniques. SOM-14 stimulated IK in a reversible manner. Continuous application of SOM-14 to the neocortical neurons led to a gradual desensitization of the SOM-14 response. Many cells became completely densensitized to SOM-14. SOM-28 also modulated IK in neocortical cells. However, SOM-28 reduced IK. This response was also reversible. Continuous application of SOM-28 to neocortical neurons led to a desensitization of the SOM-28 inhibition of IK. Many of the neurons that responded to SOM-28 became completely refractory to the peptide following prolonged SOM-28 pretreatment. While most neocortical neurons responded either to SOM-14 or to SOM-28, a population of neurons responded to both peptides. Chronic application of SOM-14 to these neurons completely desensitized the SOM-14 stimulation of IK but did not affect SOM-28 inhibition of this potassium current. Similarly, complete desensitization of SOM-28 responses in these cells was not associated with a modification of SOM-14 stimulation of IK. The lack of cross-desensitization between SOM-14 and SOM-28 induced responses suggests that these peptides act through different receptors to regulate IK.

Animals↗
PubMed1989

Biochemical properties of brain somatostatin receptors.

The physical properties of brain and pituitary somatostatin receptors were characterized using photocrosslinking techniques. Somatostatin receptors in rat corpus striatum and anterior pituitary membranes were covalently bound to the non-reducible somatostatin analog, [125I]CGP 23996, using the crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate and ultraviolet light. In striatal membranes, a protein of 60,000 mol. wt was labeled by [125I]CGP 23996. The binding was potently inhibited by somatostatin analogs but not by other biologically active peptides. The labeling of the 60,000 mol. wt protein by [125I]CGP 23996 was diminished by guanine triphosphate gamma thiol, which is consistent with the labeling of a somatostatin receptor coupled to guanine triphosphate binding proteins. The migration of the [125I]CGP 23996 labeled 60,000 mol. wt protein in native sodium dodecyl sulfate-gels was not affected by the reducing agent dithiothreitol, indicating that there is a general lack of disulfide bridges in the striatal somatostatin receptor. The striatal somatostatin receptor was solubilized with the detergent 3-[(3-cholamidopropyl)-dimethylaminoio]-1-propanesulfonate and specifically bound to the lectin wheat germ agglutinin, suggesting that the striatal somatostatin receptor is a glycoprotein. [125I]CGP 23996 also labeled a 60,000 mol. wt protein in anterior pituitary membranes. The characteristics of [125I]CGP 23996 binding to anterior pituitary membranes were consistent with the labeling of a somatostatin receptor. Interestingly, a comparison of the [125I]CGP 23996 labeled material from striatal and anterior pituitary membranes by two-dimensional polyacrylamide gel electrophoresis revealed the presence of several striatal somatostatin receptors of varying charge (pI values between 6 and 6.5) but only a single pituitary receptor. These findings indicate that physical differences may exist between subtypes of somatostatin receptors.

Animals↗
PubMed1989

Somatostatin-14 and somatostatin-28 induce opposite effects on potassium currents in rat neocortical neurons.

The prosomatostatin-derived peptides somatostatin-14 (Som-14) and somatostatin-28 (Som-28) are believed to act as neurotransmitters in the central nervous system. To examine possible mechanisms by which these peptides induce their physiological actions in brain, the effects of Som-14 and Som-28 on voltage-dependent K+ currents in rat cerebral cortical neurons in culture were examined by using whole-cell patch-clamp techniques. Som-14 increased a delayed rectifier K+ current (IK) in the cortical neurons, while Som-28 reduced IK in the neurons, both in a concentration-dependent manner. Som-14 and Som-28 could induce opposite changes in IK in the same neurons. Elevating intracellular cAMP in the cortical neurons did not modify the effects of Som-14 or Som-28 on IK, indicating that the peptides can regulate this ionic current through cAMP-independent mechanisms. Pretreatment of the neocortical cells with pertussis toxin, which inactivates inhibitory GTP-binding proteins, abolished both Som-14 and Som-28 modulation of IK, indicating that Som-14 and Som-28 receptors are coupled to IK via GTP-binding proteins. These studies show that Som-14 and Som-28 can induce opposite biological effects, suggesting that Som-14 and Som-28, acting through distinct receptors, may function as different neurotransmitters or neuromodulators.

Animals↗
PubMed1989

Purification of a putative brain somatostatin receptor.

The brain somatostatin (somatotropin release-inhibiting factor; SRIF) receptor was purified by affinity chromatographic techniques. A protein of 60 kDa could be purified from rat brain. The protein was eluted from a [D-Trp8]SRIF affinity column with either sodium acetate (pH 5.5) or free [D-Trp8]SRIF. The binding of the protein to the affinity column was prevented by free [D-Trp8]SRIF or the stable SRIF analogue SMS 201-996 but not by the inactive somatostatin 28-(1-14). The purified receptor could be covalently labeled by the 125I-labeled SRIF analogue CGP 23996. Excess [D-Trp8]SRIF blocked the binding of 125I-labeled CGP 23996 to the purified receptor, but somatostatin 28-(1-14) did not affect the binding. A 60-kDa protein was also purified from the anterior pituitary cell line AtT-20, which has a high expression of SRIF receptors. In contrast, no 60-kDa protein could be purified from CHO cells, which have no detectable SRIF receptors. These findings present evidence for the purification of the SRIF receptor.

Affinity Labels↗
PubMed1989

Protein phosphorylation induced by phorbol esters and cyclic AMP in anterior pituitary cells: possible role in adrenocorticotropin release and synthesis.

Forskolin, an activator of adenylate cyclase, stimulates adrenocorticotropin (ACTH) release and increases proopiomelanocortin mRNA levels in anterior pituitary cells by enhancing cyclic AMP (cAMP)-dependent protein kinase activity. The phorbol ester phorbol 12-myristate 13-acetate (PMA) evokes these same responses from anterior pituitary cells by activating protein kinase C. Both protein kinases most likely induce their cellular effects by catalyzing the phosphorylation of specific proteins. To elucidate the mechanisms by which cAMP-dependent protein kinase and protein kinase C promote ACTH secretion and synthesis, the phosphoproteins regulated by forskolin and PMA were identified in the cell line AtT-20, which consists of a homogeneous population of corticotrophs. Phosphoproteins were analyzed in different subcellular fractions by two-dimensional polyacrylamide gel electrophoresis and autoradiography. Forskolin increased phosphate incorporation into two proteins in the cytoplasmic fraction of 24 kilodaltons (kd) (pI 6.8) and 40 kd (pI 5.8), two proteins in the plasma membrane fraction of 32 kd (pI 8.3) and 60 kd (pI 8), and one protein in the nuclear fraction of 20 kd (pI 8.7). Insertion of the inhibitor of cAMP-dependent protein kinase into the AtT-20 cells, using a liposome technique, blocked the rise in phosphate incorporation induced by forskolin. PMA also stimulated phosphate incorporation into proteins in AtT-20 cells. PMA increased the phosphorylation of three cytoplasmic proteins of 25 kd (pI 7.6), 40 kd (pI 5.8), and 40 kd (pI 8.1) as well as two membrane proteins of 32 kd (pI 8.3) and 60 kd (pI 8) and one nuclear protein of 20 kd (pI 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Phorbol esters and corticotropin releasing factor stimulate calcium influx in the anterior pituitary tumor cell line, AtT-20, through different intracellular sites of action.

The mechanisms by which an activator of cyclic AMP-dependent protein kinase, corticotropin releasing factor (CRF) and the protein kinase C stimulant, phorbol myristate acetate (PMA) regulate the level of intracellular free calcium in the mouse anterior pituitary cell line AtT-20 were examined using the fluorescence probe Quin 2. The increase in cytosolic calcium in AtT-20 cells induced by CRF and PMA was blocked by calcium channel antagonists indicating that both agents stimulate calcium influx. The ability of PMA to raise cytosolic calcium levels was prevented by the sodium channel antagonist tetrodotoxin, suggesting that phorbol esters depolarize the cell membrane or increase action potential frequency to enhance calcium influx. The K+ channel antagonists, tetraethylammonium, cesium and 4-aminopyridine, inhibited PMA-stimulated calcium influx in AtT-20 cells. Thus, one mechanism by which protein kinase C activation may lead to a depolarization of the cell membrane is through a reduction in K+ currents. In contrast, neither tetraethylammonium or cesium reduced CRF-stimulated calcium influx into AtT-20 cells. The stimulation of calcium influx by CRF, therefore, appears to not involve changes in K+ currents in AtT-20 cells. CRF activates cyclic AMP-dependent protein kinase to stimulate calcium influx either by facilitating calcium conductance directly or by modifying the membrane potential or firing activity of AtT-20 cells.

Adrenocorticotropic Hormone↗
PubMed1989

Analogs of somatostatin selectively label distinct subtypes of somatostatin receptors in rat brain.

Somatostatin (SRIF) is a neurotransmitter in the brain. Subtypes of SRIF receptors may mediate the diverse physiological actions of SRIF in the central nervous system. In the present study, the characteristics of subtypes of brain SRIF receptors were examined using two SRIF analogs. [125I]CGP 23996 and [125I]MK 678. [125I]CGP 23996 binds selectively to rat brain SRIF receptors in a saturable manner and with high affinity. [125I]CGP 23996 binding to brain SRIF receptors is inhibited by SRIF agonists with a rank order of potency of SRIF greater than cyclo (aha-Cys-Phe-D-Trp-Lys-Thr-Cys) greater than SMS 201-995 much greater than MK 678 = L-363,301. [125I]MK 678 labels rat brain SRIF receptors which are not detected by low nanomolar concentrations of [125I]CGP 23996. [125I]MK 678 binding to brain membranes is saturable and of high affinity with a Kd of 0.3 nM and a Bmax of 217 fmol/mg of protein in brain and a Kd of 0.17 nM and a Bmax of 211 fmol/mg of protein in anterior pituitary. [125I]MK 678 binding to brain SRIF receptors is blocked selectively by SRIF analogs. SRIF, SRIF 28, D-Trp8 SRIF, SMS 201-995, cyclo (aha-Cys-Phe-D-Trp-Lys-Thr-Cys) and MK 678 have similar potencies to inhibit [125I]MK 678 binding to brain SRIF receptors. The different rank order of potencies of SRIF analogs to inhibit [125I]CGP 23996 and [125I]MK 678 binding to brain SRIF receptors suggests that these radioligands interact with different subtypes of brain SRIF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗