| 6127756 |
Pituitary somatostatin receptors: dissociation at the pituitary level of receptor affinity and biological activity for selective somatostatin analogs |
10.1016/0167-0115(82)90081-7. |
Regul Pept |
Pituitary somatostatin receptors: dissociation at the pituitary level of receptor affinity and biological activity for selective somatostatin analogs
Abstract
- High affinity and saturable binding of 125I-Tyr11somatostatin (SS) is described in membrane homogenates from a pituitary transplantable tumor (GH4C1) rich in somatotrophs (KD for SS = 0.67 nM; Bmax = 30 fmol/mg protein). Binding characteristics and pharmacology are similar to those measured on normal pituitary membranes. The potency of various SS analogs highly correlates with that measured in in vitro bioassay for growth hormone. This suggests that those GH4C1 membranes are a good model for SS receptors on somatotrophs. Interestingly however, analogs in which the Asn5 is deleted (Des-Asn5) or D-Ser replaces Ser13 show dissociated potencies between the various assays: D-Ser13 analogs are more potent in pituitary than in GH4C1 membranes binding assay. Des-Asn5-modified analogs are much more potent in both pituitary binding assays than in the bioassay. This could reflect a multiplicity of SS receptor subtypes in pituitary.
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| 6128028 |
Cation transport properties of a synthetic Ca2+-selective peptide ionophore in phospholipid and sarcoplasmic reticulum vesicles |
10.1016/0005-2736(82)90210-3. |
Biochim Biophys Acta |
Cation transport properties of a synthetic Ca2+-selective peptide ionophore in phospholipid and sarcoplasmic reticulum vesicles
Abstract
- Transport by the synthetic cyclic peptide ionophore CYCLEX-2E (Deber, C.M. Young, M.E.M., and Tom-Kun, J. (1980) Biochemistry 19, 6194-6198), which in contrast to Ca2+ ionophore A23187 contains no ionizable protons, has been studied with respect to Ca2+ and Na+ transport, and the involvement of exchanged, or counter-transported ions during the transport process. CYCLEX-2E was found to equilibrate Na+ and Ca2+ gradients across phospholipid vesicle membranes. Experiments using the indicator dye Arsenazo III established that calcium ions were indeed reaching the aqueous intravesicular compartments. Absence of metal cations in the external buffer slowed, but did not eliminate, the efflux of Ca2+ from phosphatidylcholine vesicles. As an example of its activity in a biological membrane, CYCLEX-2E was shown to be capable of producing Ca2+ efflux from sarcoplasmic reticulum vesicles which has been loaded with Ca2+ in an ATP-dependent manner. The overall results suggest that in transport by synthetic peptide ionophores typified by CYCLEX-2E, electroneutrality is achieved either through (a) peptide-mediated compensating (but not coupled) fluxes of other cations, or where this is not an option, by (b) transmembrane diffusion of permeant ions such as H+, OH-, or Cl-.
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| 6133944 |
Selective activity of cyclokinins |
10.1111/j.2042-7158.1983.tb02931.x. |
J Pharm Pharmacol |
Selective activity of cyclokinins
Abstract
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| 6135495 |
Effects of oxytocin, des-glycinamide-oxytocin and anti-oxytocin serum on the alpha-MPT-induced disappearance of catecholamines in the rat brain |
10.1016/0006-8993(83)90497-3. |
Brain Res |
Effects of oxytocin, des-glycinamide-oxytocin and anti-oxytocin serum on the alpha-MPT-induced disappearance of catecholamines in the rat brain
Abstract
- Oxytocin (OXT) attenuates memory processes and endogenous OXT might be regarded as an amnesic neuropeptide. In this study, the mode of action of OXT on brain catecholaminergic neurotransmission has been analyzed. Peripheral injection of OXT facilitated the alpha-MPT-induced disappearance of noradrenaline (NA) in the mesencephalon. Dopamine (DA) disappearance was inhibited in the mesencephalon and facilitated in the striatum. The accelerated striatal DA disappearance was not observed if the peptide was given together with alpha-MPT, but only if OXT was injected after alpha-MPT treatment. Intraventricular injection of OXT or des-glycinamide-oxytocin (DG-OXT) caused a decrease in the DA disappearance in the mesencephalon, whereas central administration of anti-oxytocin serum (anti-OXT) accelerated the DA disappearance in the same region. The data raise the possibility that DA utilization in the mesencephalon may be correlated with the influence of OXT on CNS processes.
|
| 6139329 |
Dissociated effects of somatostatin analogs on arginine-induced insulin, glucagon and growth hormone release in acromegalic patients |
10.1055/s-2007-1018762. |
Horm Metab Res |
Dissociated effects of somatostatin analogs on arginine-induced insulin, glucagon and growth hormone release in acromegalic patients
Abstract
- Two analogs of somatostatin (Ala2,D-Trp8,D-Cys14-Somatostatin and L-5F-Trp8-Somatostatin) infused into acromegalics at the rate of 4.5 micrograms/min suppressed arginine-stimulated growth hormone release more strongly than 6 micrograms/min somatostatin (110 +/- 11% and 129 +/- 14%, respectively). Under the same conditions the two somatostatin analogs induced a much smaller inhibition of insulin (33 +/- 13% and 44 +/- 18%) and glucagon (28 +/- 10% and 45 +/- 17%, respectively) release than somatostatin did. Somatostatin analogs with dissociated actions could be promising for the treatment of diseases such as acromegaly, diabetes mellitus and some ectopic hormone syndromes.
|
| 6139974 |
Rat mammary carcinoma regressions during suppression of serum growth hormone and prolactin |
None |
Anticancer Res |
Rat mammary carcinoma regressions during suppression of serum growth hormone and prolactin
Abstract
- Female rats bearing N-nitrosomethylurea-induced mammary carcinomas were treated with pergolide mesylate to suppress serum prolactin. The drug was given alone, or with somatostatin, 20 micrograms/hr delivered by osmotic minipump for 7 days to suppress serum growth hormone. Tumour regressions did not occur with pergolide alone, but did so promptly in all of 5 rats when growth hormone levels were also suppressed by somatostatin. A potent long-acting agonistic analogue of somatostatin, L362,823 produced similar tumour regressions at a dose of 5 micrograms/hr when given with pergolide, but was ineffective alone. This dose completely prevented the episodic release of pituitary growth hormone.
|
| 6143808 |
Potentiation of cyclo (N-methyl-Tyr-Arg)-induced antinociceptive activity by thyrotropin-releasing hormone in mice |
10.1111/j.2042-7158.1984.tb03018.x. |
J Pharm Pharmacol |
Potentiation of cyclo (N-methyl-Tyr-Arg)-induced antinociceptive activity by thyrotropin-releasing hormone in mice
Abstract
- The effect of thyrotropin-releasing hormone (TRH) and its metabolite, cyclo(His-Pro) (C.HP), on cyclo(N-methyl-Tyr-Arg) (C.NMTA)-induced antinociception as measured by the tail-pressure test in mice has been examined. C.NMTA-induced antinociception was significantly potentiated by simultaneously intracerebroventricular or intraperitoneal injection of TRH (approximately 20-50%) in a dose-dependent manner, whereas the effect of morphine was not influenced significantly by TRH. C.HP had no significant effect on the antinociceptive response induced by C.NMTA or morphine. It is concluded that the mechanism of C.NMTA-induced antinociception may be involved in TRH neuronal system in the brain.
|
| 6146518 |
Effect of Ala-2-D-Trp-8-D-Cys-14-somatostatin on the arginine induced release of insulin, GH and glucagon in normal men |
10.1080/07435808409046764. |
Endocr Res |
Effect of Ala-2-D-Trp-8-D-Cys-14-somatostatin on the arginine induced release of insulin, GH and glucagon in normal men
Abstract
- The effects of several doses of somatostatin (SS) and the analog Ala-2-D-Trp-8-D-Cys-14-SS on the arginine-induced release of insulin, glucagon, and GH were compared in a group of normal human subjects. Somatostatin suppressed the release of insulin, glucagon and GH when administered in a dose of 100 micrograms/hr. The same dose of Ala-2-D-Trp-8-D-Cys-14-SS inhibited GH and glucagon release, but although insulin levels were decreased about 24%, this inhibition was not significant statistically. Higher doses of Ala-2-D-Trp-8-D-Cys-14-SS (300 micrograms/hr) induced a partial inhibition of insulin secretion and completely blocked GH release. These results indicate that in humans this analog is a less potent inhibitor of insulin release than somatostatin.
|
| 6148950 |
Conformational aspects of the molecular mechanism of action of bradykinin. II. Conformation and selectivity of action of bradykinin cycloanalogs |
None |
Bioorg Khim |
Conformational aspects of the molecular mechanism of action of bradykinin. II. Conformation and selectivity of action of bradykinin cycloanalogs
Abstract
- Conformation energy calculations performed for cyclo(epsilon-lysine1, glycine6)bradykinin and cyclo-epsilon-kallidin indicate the absence of spatially equivalent low-energy structures for bradykinin and cyclobradykinin molecules, whereas cyclokallidin has conformations similar to the "biologically active" ones for bradykinin that are implicated in binding to both B1 and B2 type receptors.
|
| 6150052 |
Suppression and stimulation of growth hormone release in sheep by somatostatin analogs |
10.1007/BF03351002. |
J Endocrinol Invest |
Suppression and stimulation of growth hormone release in sheep by somatostatin analogs
Abstract
- The inhibitory and stimulatory effects of somatostatin analogues on growth hormone secretion have been studied in the sheep. Plasma immunoreactive growth hormone (GH) was stimulated by the iv administration of the antilipolytic compound 3,5-dimethylpyrazole and was followed by infusion of somatostatin (SRIF) and analogues into the carotid artery. The analogues D-trp8-D-cys14-SRIF, des-AA1,2,4,5,12D-trp8-D-cys-14SRIF, and SRIF-Wy 40793 were shown to cause a dose-dependent suppression of plasma GH, followed by a significant rise ("rebound") on terminating the infusion. In general, the greater the suppression, the greater the rebound. A significant correlation between the rebound increase in plasma GH and dose of both SRIF and des-AA1,2,4,5,12D-trp8-cys14-SRIF was demonstrated (p less than 0.01 and p less than 0.001, respectively). This analogue and Wy-40793 showed a significantly greater rebound than did SRIF following 50% suppression of the GH response (p less than 0.01 and p less than 0.05, respectively). Although two analogues were shown to be significantly more potent than SRIF (p less than 0.01), in this sheep bioassay the duration of action did not appear to be longer than that of the native hormone for any of the three analogues.
|
| 6150467 |
Cyclic hexa- and pentapeptide somatostatin analogues with reduced gastric inhibitory activity |
10.1016/0196-9781(84)90106-2. |
Peptides |
Cyclic hexa- and pentapeptide somatostatin analogues with reduced gastric inhibitory activity
Abstract
- The gastric inhibitory activity of cyclic hexa- and pentapeptide analogues of somatostatin was investigated in conscious cats with gastric fistulae. Gastric acid and pepsin secretions were stimulated by pentagastrin. Cyclo(Phe-Phe-D-Trp-Lys-Thr-Phe) showed no inhibition of acid secretion at molar doses up to 50-times the ID50 for somatostatin. This peptide inhibited pepsin secretion at the highest dose (50 micrograms kg-1 hr-1), and its potency is approximately 0.005 compared with somatostatin (1.0). Cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) inhibited acid (approximately 50%) and pepsin (approximately 85%) secretions, but the inhibition was not dose-related being similar with doses of 10 to 50 micrograms kg-1 hr-1. The cyclic pentapeptide, cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr), was inactive in the dose range studied, with a potency less than 0.01. Cyclo7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl) has been described as a somatostatin antagonist with respect to inhibition of growth hormone, insulin and glucagon release in rats 2. Up to 60-fold molar excesses of this peptide failed to antagonise the inhibitory activity of somatostatin in the stomach. The results demonstrate that residues outside the central 6-11 region of somatostatin are very important for its gastric activity. The lack of gastric antagonistic activity of the pentapeptide antagonist indicates that these residues are likely to be involved in receptor recognition/binding.
|
| 6150528 |
Selective inhibition of sleep related growth hormone release by Phe-4-somatostatin |
None |
Res Commun Chem Pathol Pharmacol |
Selective inhibition of sleep related growth hormone release by Phe-4-somatostatin
Abstract
- We have compared the effects of somatostatin (SS) and the somatostatin analog Phe-4-SS on nocturnal GH secretion in three normal male volunteers, 20 to 23 years of age. Subjects were studied in our sleep laboratory on 5 consecutive nights. Nights 1 and 2 were used for adaptation. On the third night (control night), all patients exhibited a typical GH peak accompanying slow-wave sleep, with maximum GH levels from 9.2 to 27 ng/ml. Insulin, glucagon and glucose levels were episodic and sleep-independent. On night 4, subjects received SS infusion at a rate of 3 micrograms/min, which inhibited GH levels consistently below 2.4 ng/ml. In two cases a post-infusion rebound of GH levels was observed. During SS infusion all three subjects showed a significant decrease in insulin levels (p less than 0.0005), followed by an immediate rebound after infusion was stopped. Glucagon levels fell significantly during infusion (p less than 0.001, p less than 0.025 and p less than 0.00025 respectively). Glucose was significantly higher than on control night in subject No. 3 (p less than 0.0005) and similar to control night in subjects 1 and 2. On the fifth night, Phe-4-SS was infused at a rate of 0.75 microgram/min. GH levels decreased significantly as compared to control night in all three subjects and remained virtually constant throughout the night. Insulin levels were diminished in subject No. 1 (p less than 0.0005), but were comparable to control values in subjects 2 and 3. Cessation of analog infusion was followed by a rebound in insulin levels in all three subjects. Glucagon values were not significantly lowered and the rebound effect was not apparent. Glucose levels were higher in response to Phe-4-SS than on control night, and fell below infusion values (p less than 0.001) after administration was discontinued. It was concluded that Phe-4-SS inhibits nocturnal secretion of GH more selectively than SS, but its effect is not more prolonged than that of SS.
|
| 6150529 |
Inhibition of growth hormone and glucagon release by Phe-4-somatostatin in patients with acromegaly |
None |
Res Commun Chem Pathol Pharmacol |
Inhibition of growth hormone and glucagon release by Phe-4-somatostatin in patients with acromegaly
Abstract
- We have studied growth hormone (GH), insulin (I), glucagon (Gl) and glucose in basal conditions, after somatostatin (SS) (3 micrograms/ml) and Phe-4-SS (0.75 microgram/ml) infusion and IV bolus of the latter in 3 acromegalic patients. In two patients, Phe-4-SS inhibited glucagon and growth hormone secretion in a similar way as SS, without modifying insulin secretion. These effects were short-lived and ceased after the infusion was stopped. From these results it appears that Phe-4-SS is both more potent and more specific than SS with respect to inhibition of GH and glucagon release, but it does not have prolonged biological action. Lack of suppression of GH by SS or Phe-4-SS in the acromegalic patient with post-surgical recurrence of the disease could be due to the existence of receptor abnormalities, and suggests a diversity in the physiopathology of the disease.
|
| 6151906 |
Urinary excretion of free catecholamines in long-term treatment with dopaminergic agonists |
10.1055/s-0029-1210385. |
Exp Clin Endocrinol |
Urinary excretion of free catecholamines in long-term treatment with dopaminergic agonists
Abstract
- Urinary excretion of free adrenaline, noradrenaline and dopamine was examined in 12 patients with active acromegaly before and during long-term therapy (6-22 months) with ergoline derivatives bromocriptine (20-30 mg daily) and lisuride (1-2 mg daily). A significant fall in noradrenaline values (4.5 +/- 0.95 (SEM) nmol/h on v.s. 15.3 +/- 3.8 nmol/h before the treatment, P less than 0.01) was found in the treated patients. Adrenaline excretion rose in most patients but the difference was not significant (1.43 +/- 0.33 nmol/h on v.s. 1.02 +/- 0.36 nmol/h before the treatment, P greater than 0.05). No significant change was seen in the dopamine excretion (71.3 +/- 9.58 nmol/h on v.s. 75.0 +/- 7.0 nmol/h before the treatment, P greater than 0.05). Our studies confirm the blood pressure lowering effect of bromocriptine and lisuride even when used on a long-term basis. This effect seems to be associated with reduced sympathetic activity.
|
| 6152065 |
Pharmacokinetics, distribution and elimination of a synthetic octapeptide analogue of somatostatin in the rat |
10.1016/0167-0115(84)90073-9. |
Regul Pept |
Pharmacokinetics, distribution and elimination of a synthetic octapeptide analogue of somatostatin in the rat
Abstract
- The in vivo fate of a long acting somatostatin analogue des-AA1,2,3,4,13,14,D-Trp8,Gaba12-somatostatin has been studied in the rat using biochemical and autoradiographic techniques. The analogue has a longer plasma half-life than somatostatin. This is due to its greater metabolic stability which renders it resistant to enzymic attack in the tissues. The primary route of elimination is by biliary excretion following clearance from the circulation by the liver. Evidence of enterohepatic circulation was found, but only to a very limited extent. When administered s.c., high plasma concentrations of intact peptide persist for a period of hours due to slow release from a stable depot at the injection site.
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