(D-Phe12) bombesin and substance P analogues function as central bombesin receptor antagonists

Z. Merali, C. A. Merchant, Jacqueline Crawley, D. H. Coy, P. Heinz-Erian, R. T. Jensen, T. W. Moody

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The potency of synthetic bombesin (BN) analogues with D-Phe12 substitutions and substance P analogues was investigated in the rat CNS. (D-Phe12,Leu14)BN, (D-Phe12)BN and (Tyr4,D-Phe12)BN inhibited binding to rat brain slices with IC50 values of approximately 2 μM. Similarly, spantide inhibited binding to rat brain slices with an IC50 value of 1.5 μM. Spantide inhibited specific (125I-Tyr4)BN binding as a result of decreased rate of association, whereas the rate of dissociation was unaffected. Neither the (D-Phe12)BN analogues nor the substance P analogues inhibited specific binding of 125I-VIP to rat brain slices. Central administration of BN (0.5 μg) induced grooming and suppressed feeding and resting. (Tyr4, D-Phe12)BN (5 μg) antagonized the behavioral effects of BN. Although spantide (2 μg) also antagonized many of the BN effects, it had intrinsic effects and hence the behavioral antagonism was not specific. These data suggest that although both (D-Phe12)BN and substance p analogues may function as central BN receptor antagonists, the (D-Phe12)BN analogues may be functionally the more useful class of antagonists.

Original languageEnglish (US)
Pages (from-to)282-287
Number of pages6
JournalSynapse
Volume2
Issue number3
StatePublished - 1988
Externally publishedYes

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ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)
  • Pharmacology

Cite this

Merali, Z., Merchant, C. A., Crawley, J., Coy, D. H., Heinz-Erian, P., Jensen, R. T., & Moody, T. W. (1988). (D-Phe12) bombesin and substance P analogues function as central bombesin receptor antagonists. Synapse, 2(3), 282-287.