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W Haq

Publications and source records attributed to W Haq.

46 records · Page 3Linked to original sources
PubMed1995

Novel met-enkephalin analogue: a potent systemic mu agonist antinociceptive agent.

A new met-enkephalin analogue (compound 82/205) was evaluated for its opioidergic activity in mice. The compound showed antinociception (warm water tail-flick test), tolerance, cross tolerance to morphine and physical dependence. The time course of antinociceptive effect of the compound was comparable to morphine. The antinociceptive ED50 (mumol kg-1, i.p.) values for the compound and morphine base were 5.31 and 7.59, respectively. Its antinociceptive effect was blocked by naloxone, beta-FNA (mu antagonist) and naloxonazine (mu1 antagonist) but not by ICI 174,864 (delta antagonist). Naloxone precipitated withdrawal jumpings were 2.6 times less in compound 82/205 treated mice than the morphine treated group. The new analogue compound 82/205 is a potent mu agonist antinociceptive with a possible weak dependence liability.

Analgesics↗
PubMed1993

Augmentation of human natural killer cells by splenopentin analogs.

Splenopentin, Arg-Lys-Glu-Val-Tyr (SP-5) and its synthetic analogs; Arg-D-Lys-Glu-Val-Tyr (pentapeptide 1), Lys-Lys-Glu-Val-Tyr (2), D-Lys-Lys-Glu-Val-Tyr (3), Arg-Lys-Gly-Val-Tyr (4), and Arg-Lys-Gln-Val-Tyr (5) have been examined for augmentation of human natural killer (NK) cell activity and human T-cell transformation response. Pentapeptides 2 and 3 were found to significantly augment the in vitro human NK cell activity. However, none of them had any effect on lymphocyte proliferative responses.

Adjuvants, Immunologic↗
PubMed1993

Enkephalin antisense peptides: design, synthesis, and biological activity.

The antisense mRNA complementary to the sense strand of Metenkephalin encodes the antisense peptides, His-Glu-Ala-Pro-Ile (compound 88/62). The antisense peptide and its (Gln1)-analogue (compound 88/63) have synergestic effects on the opioid activity of Met-enkephalin in the GPI test system.

Amino Acid Sequence↗
PubMed1993

Immunostimulant activity of a novel lipopeptide and its protective action against Leishmania donovani.

Novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated antibody and delayed type hypersensitivity (DTH) response to ovalbumin in guinea pigs. Lipopeptide 86/450 also stimulated antibody and DTH responses in albino mice and enhanced nonspecifically macrophage migration index (MMI), phagocytic activity and incorporation of [14C] glucosamine in peritoneal macrophages of the treated animals. Proliferative response of splenocytes from lipopeptide 86/450 treated animals was significantly higher than that from untreated controls. Peritoneal macrophages from lipopeptide 86/450 treated mice were less susceptible to Leishmania donovani promastigote invasion when co-cultured in vitro. The treated animals on challenge with L. donovani promastigote/amastigote showed 80 to 90% lower intake of infection than the control animals.

Adjuvants, Immunologic↗
PubMed1991

Adjuvant activity of some nonpyrogenic hydrophobic analogues of muramyl dipeptide in enhancing the primary humoral and cell mediated immune responses in guinea pig model.

Five muramyl dipeptide analogues synthesized by derivatization of gamma-carboxyl of D-isoglutamine residue of MDP into alkyl amides or incorporation of lysine residue at the site via epsilon-NH2 function were evaluated for immuno-adjuvant activity. Derivatization of gamma-carboxyl of D-isoglutamine into butyl, octyl and dibutyl residues stimulated delayed type of hypersensitivity (DTH) response, the maximum stimulation being observed with octyl amide. Introduction of lauryl amide residue abolished DTH response. The antibody response was impaired with all the alkyl amide analogues except for the lysyl amide derivative with which the response was higher than MDP. Correlation was observed between DTH response and macrophage migration.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Lymphokines production by concanavalin A-stimulated mouse splenocytes: modulation by Met-enkephalin and a related peptide.

Methionine-enkephalin (ME) and its synthetic congener Tyr-D-Ala-Gly-Me-Phe-Gly-NH.C3H7-iso (82/205), in a concentration-dependent biphasic manner modulated the concanavalin A (Con A)-stimulated phagocytosis-promoting (PP)-activity elaboration in the culture supernatants of mouse splenocytes in vitro. Both these peptides at 1 x 10(-5) and 1 x 10(-6) M inhibited the production of PP activity; conversely, at 1 x 10(-7)-1 x 10(-9) M they augmented it. Peptide 82/205 was nearly 1.2-fold more inhibitory and approximately 1.8-fold more potent in augmenting the PP activity elaboration. The PP activity appeared to be due to lymphokines (LK) gamma interferon and interleukin-4 as the neutralizing concentrations of monoclonal antibodies against these LK significantly (p < 0.05) inhibited it. Cycloheximide (50.0 micrograms/ml) completely inhibited the production of LK indicating their de novo synthesis. The peptides appeared to exert their inhibitory and augmenting effects via delta- and mu-opioid receptors, respectively, as pretreatment of splenocytes with 100-fold higher (1 x 10(-3) M) concentration of naloxone was required to block their inhibitory effect; the augmenting effect was blocked by 1 x 10(-5) M only. None of the peptides or naloxone could directly stimulate the splenocytes for PP-LK elaboration.

Amino Acid Sequence↗
PubMedDate not supplied

Delta-opioid receptor antagonist inhibits immunomodulation by Met-enkephalin analogs.

The methionine-enkephalin (Met-enkephalin, Tyr-Gly- Gly-Phe-Met) analogs Tyr-D-Ala-Gly-MePhe-Met NHC(3)H(7)-iso (1) and Tyr-D-Ala-Gly-MePhe-Gly-NHC(3)H(7)-iso (2) have been shown to enhance human T cell proliferation in in vitro treatment. Their immunomodulatory activities were completely blocked by naloxone, an opioid antagonist. Now we demonstrate that a selective delta-opioid receptor antagonist, ICI-174,864, completely blocks enhancement of T cell proliferation by analogs (1) and (2). The T cell-stimulatory effect was only partially inhibited by the mu-receptor-selective antagonist, beta-funaltrexamine hydrochloride. The kappa-opioid receptor antagonist, nor-binaltorphimine dihydrochloride, showed no effect on T cell-proliferation stimulated by analogs (1) and (2). These observations suggest that analogs (1) and (2) of Met-enkephalin stimulate T cell proliferation predominantly via delta-opioid receptor present on T cells.

Adjuvants, Immunologic↗
PubMedDate not supplied

Molecular biology of opioid receptors: recent advances.

Endogenous opioid peptides and opiates like morphine produce their pharmacological effects through the membrane bound opioid receptors. These receptors belong to a superfamily of G-protein-coupled receptors, all of which possess seven membrane-spanning regions. Structure-activity relationship studies of opioids opened up new avenues for the pharmacological characterization of the opioid receptors. As a further advancement in this direction, molecular cloning has led to the identification of three different types of opioid receptors -- OP1 (delta), OP2 (kappa) and OP3 (mu) -- thereby supporting the results of earlier pharmacological studies which postulated their existence. The three opioid receptors are highly homologous. Consequent to the development of highly specific and selective agonists and antagonists, it was proposed that the three types of opioid receptors could be further categorized into different subtypes. However, the molecular biology data generated so far do not support the presence of the various subtypes of the three well-characterized opioid receptors. Recent strides towards the advancement of our knowledge relating to the molecular biology of these receptors have been reviewed in this article.

Animals↗
PubMedDate not supplied

Enkephalins-modulation of Plasmodium cynomolgi antigens-induced colony-stimulating factors elaboration by macrophages.

Methionine-enkephalin (M-Enk) and its analogue compound 82/205 (10(-5) and 10(-6) M) inhibited elaboration of Plasmodium cynomolgi total antigens soluble in culture medium (P.c.SA)-induced colony-stimulating factors (CSFs) by monkey blood monocyte-derived macrophages, in vitro. Paradoxically, lower concentrations (10(-7)-10(-9) M) of both the peptides greatly augmented CSFs elaboration; 82/205 appeared to be nearly 2.3-fold more potent. Naloxone (10(-5) M) pretreatment of macrophages inhibited only the M-Enk- and 82/205-induced enhanced CSFs elaboration, suggesting an opiate receptors-mediated mechanism of action. None of the peptides or naloxone (10(-5)-10(-9) M) had any direct effect on the CSF elaboration by unstimulated macrophages.

Animals↗