Antimicrobial and antiviral activity of xylosyl-methylthio-adenosine,a naturally occurring analogue of methylthio-adenosine fromDoris verrucosa

Xylosyl-methylthio-adenosine, a naturally occurring analogue of 5′-deoxy-5′-methylthio-adenosine, has been postulated to play a protective role during egg development in the molluscDoris verrucosa. However, in vitro tests showed that this analogue is devoid of activity against fungi, bacteria and viruses.     

The effect of a bradykinin antagonist on vasodilator responses with particular reference to the submandibular gland of the cat

Summary A bradykinin analogue, D-Arg[Hyp³, Thi^{5, 8}, D-Phe⁷]-Bk, antagonized the vasodilator effect of bradykinin injected close-arterially in the submandibular salivary gland of the cat, without affecting that due to acetylcholine or nerve stimulation. The same analogue also antagonized the hypotensive response to bradykinin injected intravenously in cats and rabbits. We conclude that functional hyperaemia in the submandibular gland of the cat is not due to the release of bradykinin by salivary kallikrein.     

Synthesis of O1.5-(beta-D-galactopyranosyl) [DMet2, Hyp5] enkephalin amide, a new highly potent analgesic enkephalin-related glycosyl peptide

A new series of O-glycosyl enkephalins has been prepared, following a convergent strategy, with high chemical yields. The galactosyl analogue, O1.5-(beta-D-galactopyranosyl) [DMet2, Hyp5] enkephalin amide proved to be one of the most potent in vivo opioid agonists synthesized up to now.     

5-Bromodeoxyuridine inhibition of the transformation of Rous sarcoma virus-infected chicken cells]

The transformation of Rous-Sarcoma-Virus-infected synchronized Chicken cells is prevented when 5-bromodeoxyuridine is added for 3 hrs. at time of the peak of the first S phase following infection. Virus progeny is normally released. The inhibitory effect of BrdU is reversed by simultaneous addition of thymidine, but not by that of deoxyuridine. Hence, the inhibition of the transformation seems to result from the incorporation of the analogue into the nuclear DNA.     

Alpha-hydrazinophloretic acid, competitive inhibitor of fungal tyrosinase]

alpha-Hydrazinophloretic acid, the hydrazino analogue of tyrosine, was shown to behave as a competitive inhibitor of tyrosinase. Some closely related compounds, especially the hydrazino analogue of phenylalanine as well as other hydrazine derivatives, will also inhibit the enzyme, but in these cases, the inhibition observed belonged to the non-competitive type.     

Differential effects of calcium channel blockers on the responses of the rat vas deferens to intramural nerve stimulation and exogenous drugs

Summary The calcium channel blockers, nifedipine and verapamil, have separate effects on the phases of nerve-induced twitches which are not reflected by their actions on the responses to exogenous NA, ATP and the stable ATP analogue, ,-mATP. This implies that different calcium channels are used according to the manner of stimulation.     

The action of the cholecystokinin-A receptor antagonist,devazepide, on the digestive system of the chicken

The influence of the cholecystokinin (CCK)-A receptor antagonist, devazepide (DVZ), on the chicken digestive tract was investigated. The passage of food from the crops of birds treated with DVZ was not significantly different from that of the control. DVZ treatment did not inhibit the biliary flow stimulated by the CCK analogue, caerulein. Dispersed chicken pancreatic acini stimulated with CCK were treated with various concentrations of DVZ. At 10^–5 M, DVZ completely inhibited amylase release; this concentration was much higher than those reported to have similar effects in mammals. The results suggest that the action DVZ as a CCK antagonist in the chicken is very weak.     

Effect of administration of synthetic ecdysone on the moulting ofPalamnaeus bengalensis

Summary Synthetic analogue of ecdysone, 3, 14-dihydroxy-5-cholest-7-en-6-one did not bring the scorpionPalamnaeus bengalensis to moult. It also failed completely in stimulating the scorption to produce any change related to moulting.Acknowledgment. Author is grateful to Dr Suresh C. Shrivastava for providing research facilities, Dr S.P. Tewarson for encouragement and S.C.S.T. (U.P.) for funds. Present address: Department of Zoology, Lucknow Christian College, Lucknow-226001.     

The effect of a bradykinin antagonist on vasodilator responses with particular reference to the submandibular gland of the cat

A bradykinin analogue, D-Arg[Hyp3, Thi5,8, D-Phe7]-Bk, antagonized the vasodilator effect of bradykinin injected close-arterially in the submandibular salivary gland of the cat, without affecting that due to acetylcholine or nerve stimulation. The same analogue also antagonized the hypotensive response to bradykinin injected intravenously in cats and rabbits. We conclude that functional hyperaemia in the submandibular gland of the cat is not due to the release of bradykinin by salivary kallikrein.     

Synthesis ofO 1.5-(β-D-galactopyranosyl) [DMet2, Hyp5] enkephalin amide,a new highly potent analgesic enkephalin-related glycosyl peptide

Summary A new series of O-glycosyl enkephalins has been prepared, following a convergent strategy, with high chemical yields. The galactosyl analogue,O ^1.5-(-D-galactopyranosyl) [DMet², Hyp⁵] enkephalin amide proved to be one of the most potent in vivo opioid agonists synthesized up to now.     

Hypotensive activity of histidine-containing analogues of C-terminal hexapeptide of substance P

Four new hexapeptide analogues of C-terminal Substance P fragment with increased solubility in aqueous solutions are described. The peptides contain histidine in positions 6, 8, 9 and 10, respectively. The effect of the structural changes on the hypotensive activity and antigenic properties of analogues was compared. It was found that substitution of amino acid residues in various positions in the C-terminal hexapeptide of Substance P resulted in different effects on the hypotensive and antigenic properties, respectively. Only the [His6] SP6-11 analogue had an unchanged antigenic structure when compared with the C-terminal region of Substance P, but it showed an almost total loss of hypotensive activity. The [His9] SP6-11 analogue retained 50% of the hypotensive activity of the C-terminal hexapeptide but showed a markedly reduced expression of the antigenic epitope localized in this region of Substance P.     

Opposite effects of beta-adrenoceptor stimulation and 8-bromo-cyclic AMP on potassium efflux in mammalian heart muscle

beta-adrenoceptor stimulation by isoprenaline increases the potassium efflux in beating guinea-pig atria. This effect is not mimicked by 8-bromo-cyclic AMP, a cyclic AMP analogue which exerts a positive inotropic effect in this preparation.     

Directed biosynthesis of analogues of ergot peptide alkaloids with Claviceps purpurea

Analogues of peptide ergot alkaloids can be obtained by feeding a producing culture of Claviceps purpurea with an analogue of one of the amino acids of the peptide chain of the alkaloid.     

Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity

Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E1 analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation.     

Prostaglandin analogue protects pancreatic B-cells against cyclosporin A toxicity

Summary Cyclosporin A toxicity on pancreatic B-cells and its prevention by rioprostil, a prostaglandin E₁ analogue, were studied in the model of the isolated perfused pancreas of rats treated with both compounds for 8 days. At toxic doses of cyclosporin (10 and 20 mg/kg b.wt), the B-cells showed severe hydropic degeneration of the endoplasmatic reticulum and slight degranulation of the B-cells. Accordingly, the insulin secretion was markedly impaired. Administration of rioprostil ameliorated the insulin secretion significantly, but not the ultrastructural changes. At therapeutic levels of cyclosporin (5 mg/kg b.wt), the hydropic degeneration and the drop in insulin secretion were completely prevented by rioprostil. This observation might have therapeutic implications in the treatment of patients, in particular those undergoing pancreatic transplantation.     

Directed biosynthesis of analogues of ergot peptide alkaloids withClaviceps purpurea

Summary Analogues of peptide ergot alkaloids can be obtained by feeding a producing culture ofClaviceps purpurea with an analogue of one of the amino acids of the peptide chain of the alkaloid.     

Hypotensive activity of histidine-containing analogues of C-terminal hexapeptide of Substance P

Summary Four new hexapeptide analogues of C-terminal Substance P fragment with increased solubility in aqueous solutions are described. The peptides contain histidine in positions 6, 8, 9 and 10, respectively. The effect of the structural changes on the hypotensive activity and antigenic properties of analogues was compared. It was found that substitution of amino acid residues in various positions in the C-terminal hexapeptide of Substance P resulted in different effects on the hypotensive and antigenic properties, respectively. Only the [His⁶] SP_6-11 analogue had an unchanged antigenic structure when compared with the C-terminal region of Substance P, but it showed an almost total loss of hypotensive activity. The [His⁹] SP_6-11 analogue retained 50% of the hypotensive activity of the C-terminal hexapeptide but showed a markedly reduced expression of the antigenic epitope localized in this region of Substance P.     

Differentiating effects of the glucagon-like peptide-1 analogue exendin-4 in a human neuronal cell model

Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide with neurotrophic properties, as assessed in animal cell models. Exendin-4, a GLP-1 analogue, has been recently approved for the treatment of type 2 diabetes mellitus. The aim of this study was to morphologically, structurally, and functionally characterize the differentiating actions of exendin-4 using a human neuronal cell model (i.e., SH-SY5Y cells). We found that exendin-4 increased the number of neurites paralleled by dramatic changes in intracellular actin and tubulin distribution. Electrophysiological analyses showed an increase in cell membrane surface and in stretch-activated-channels sensitivity, an increased conductance of Na⁺ channels and amplitude of Ca⁺⁺ currents (T- and L-type), typical of a more mature neuronal phenotype. To our knowledge, this is the first demonstration that exendin-4 promotes neuronal differentiation in human cells. Noteworthy, our data support the claimed favorable role of exendin-4 against diabetic neuropathy as well as against different neurodegenerative diseases.     

Potentiation of ethanol narcosis by dopamine- and l-DOPA-based isoquinolines.

The isoquinolines, salsolinol and 3-carboxysalsolinol, prolong ethanol-induced narcosis in mice. Pretreatment with carbidopa increases the effect of 3-carboxysalsolinol but not of salsolinol. These results suggest that ethanol sleeping-time potentiation by l-LOPA may involve a partial conversion to the isoquinoline in vivo. A central depressant action of salsolinol or the 3-carboxy analogue is suggested.     

Changes in patterns of ecdysteroid secretion by the ring gland ofDrosophila in relation to the sterol composition of the diet

Summary Brain-ring glands fromDrosophila larvae reared on a defined diet containing campesterol (24-methyl-cholesterol) as the major sterol, secreted-in addition to ecdysone-a compound identified previously as a 24-methyl analogue, 20-deoxy-makisterone A. Using ergosterol or cholesterol as the sterol component of the diet, only ecdysone was detectable in cultures of brain-ring glands.