Mast cell histamine secretion in response to somatostatin analogues: structural considerations

European Journal of Pharmacology
T C Theoharides, W W Douglas

Abstract

Comparative studies of the activity of somatostatin and of several of its analogues in releasing histamine from rat mast cells suggest that the integrity of the positively charged amino terminus and of lysines at positions four and nine of somatostatin may be necessary to preserve its histamine releasing activity. D-Lys4 substitution reduced activity by 80% while D-Lys9 substitution increased it four fold. Replacement of the amino terminal Ala by Tyr or simultaneous removal of Ala1,Gly2 and the amino portion of the now terminal Cys3 inhibited the activity by about 95%. Finally, dihydrosomatostatin retained 33% activity while an analogue where both Cys sulfur atoms were permanently blocked by acetamidomethyl groups retained only about 13% activity. Using information from these studies and from the literature, two-dimensional and space-filling models approximating the conformation of somatostatin were constructed and compared with a plausible corresponding model of the hexameric form of 48/80, the most active congener of this classic mast cell secretagogue. By such modelling it was possible to show that the orientation of the cationic moieties in the two molecules could be similarly arranged thereby perhaps explaining the ability...Continue Reading

References

Jan 1, 1978·Annual Review of Biochemistry·A V SchallyC A Meyers
Feb 15, 1978·Biochemical Pharmacology·J H Baxter, R Adamik
May 1, 1978·Endocrinology·T C Theoharides, W W Douglas
Nov 1, 1977·Biochemistry·L A HolladayD Puett
Apr 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·L A Holladay, D Puett
Jul 28, 1972·Science·E Habermann
Apr 1, 1973·Proceedings of the Society for Experimental Biology and Medicine·A R Johnson, E G Erdös
Mar 1, 1972·Journal of Medicinal Chemistry·G W Read, J F Lenney
Jan 16, 1981·European Journal of Pharmacology·T C TheoharidesW W Douglas
Jun 24, 1961·Biochimica Et Biophysica Acta·L T KREMZNER, I B WILSON
Nov 1, 1970·The Journal of Cell Biology·J Padawer

❮ Previous
Next ❯

Citations

Mar 1, 1993·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·M Sosnowski
Dec 1, 1985·Naunyn-Schmiedeberg's Archives of Pharmacology·W Piotrowski, J C Foreman
May 28, 1992·Biochemical Pharmacology·H VliagoftisT C Theoharides
Apr 27, 1988·European Journal of Pharmacology·P DevillierD Regoli
Aug 1, 1990·Journal of Reproductive Immunology·P PöllänenO Söder
May 1, 1994·Journal of Reproductive Immunology·P Pöllänen, T G Cooper
Sep 29, 1999·International Journal of Immunopharmacology·H VliagoftisT C Theoharides
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K FolkersS Leander
Feb 1, 1994·European Journal of Clinical Investigation·P M van HagenS W Lamberts
Jan 1, 1990·Annals of the New York Academy of Sciences·D L BellingerD L Felten
Jan 11, 2005·Rheumatic Diseases Clinics of North America·Hans-Georg SchaibleMarco Matucci-Cerinic
Jan 1, 1987·Annals of the New York Academy of Sciences·D G Payan, E J Goetzl
Jan 1, 1987·Annals of the New York Academy of Sciences·D G PayanE J Goetzl
Jan 1, 1988·The International Journal of Neuroscience·D G Payan, E J Goetzl
Jun 1, 1992·Journal of Protein Chemistry·A BukuD Gazis
Nov 1, 1988·Immunological Investigations·G Marone
Nov 1, 1994·International Journal of Peptide and Protein Research·A BukuK Polewski
Nov 1, 1995·Arthritis and Rheumatism·M Matucci-CerinicP Marinelli
May 1, 1991·The Journal of Investigative Dermatology·J GutwaldC Sorg
Aug 9, 1982·Life Sciences·S S Rossie, R J Miller
Jan 15, 1983·Biochemical Pharmacology·N D TsakalosP W Askenase
Jul 15, 1982·Biochemical Pharmacology·L M PattJ C Houck
Sep 15, 1985·Biochemical Pharmacology·T B CasaleM Kaliner
Aug 1, 1996·Metabolism: Clinical and Experimental·D E Elliott, J V Weinstock
Jan 1, 1987·Journal of Neuroscience Research·F K RenoldD G Payan
Jun 1, 1982·Pharmacological Research Communications·A Bruni, G Toffano

❮ Previous
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