High potency of a new bombesin antagonist (RC-3095) in inhibiting serum gastrin levels; comparison of different routes of administration

Jacek Pinski, Tetsu Yano, Zoltan Rekasi, Renzhi Cai, Sinisa Radulovic, Andrew V. Schally

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

This study was performed to evaluate the efficacy and duration of action of a new bombesin antagonist d-Tpi6,Leu13 ψ (CH2NH)Leu14-bombesin (6-14) (RC-3095), given by different routes of administration, in suppressing gastrin releasing-peptide (GRP(14-27))-stimulated gastrin release in rats. First, we showed that GRP(14-27) itself was highly active when administered by different routes. GRP(14-27), given to rats at a dose of 25 μg/100 g b.w. significantly increased serum gastrin levels 3 and 6 min after intravenous and for more than 30 min after subcutaneous administration or pulmonary inhalation. RC-3095 was then injected subcutaneously, intravenously and also delivered by pulmonary inhalation at a dose of 10 μg/100 g b.w. in each case to seven male rats 2, 30, 60 or 120 min prior to i.v. administration of 5 μg GRP(14-27). RC-3095 administered 2 min prior to GRP(14-27) decreased the gastrin response to GRP(14-27), measured as area under the curve, by 81% in the intravenously injected group and 64% in the pulmonary inhalation group in the first 6 min. When GRP(14-27), was given 30 min after administration of RC-3095, the gastrin response was decreased by 52% in the subcutaneous group, 49% in the pulmonary inhalation group and 11% in the intravenous group during the first 6 min. RC-3095 delivered subcutaneously or by pulmonary inhalation 1 h before GRP(14-27) was also able to significantly inhibit gastrin release. Analysis of the data revealed that the biovailability of RC-3095 given by the pulmonary inhalation route was about 69% of the s.c. route. Our results indicate high activity of bombesin antagonist RC-3095, administered by different in vivo routes, in suppressing serum gastrin in rats. The administration by pulmonary inhalation evaluated here in rats, may prove to be practical and useful in the clinical setting.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalRegulatory Peptides
Volume41
Issue number3
DOIs
StatePublished - Oct 13 1992
Externally publishedYes

Keywords

  • Bombesin antagonist
  • Gastrin
  • Pulmonary inhalation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

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