Premium
Mediation by SRIF 1 receptors of the contractile action of somatostatin in rat isolated distal colon; studies using some novel SRIF analogues
Author(s) -
McKeen E.S.,
Feniuk W.,
Humphrey P.P.A.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17036.x
Subject(s) - medicine , somatostatin , endocrinology , agonist , somatostatin receptor , chemistry , receptor , somatostatin receptor 2 , biology
1 The motor effects of somatostatin‐14 (SRIF), and several SRIF peptide analogues were investigated on the rat isolated distal colon. The objective of these studies was to characterize the receptor mediating the contractile action of SRIF by comparing the relative agonist potencies of a range of SRIF analogues. 2 SRIF (1 n m ‐1 μ m ) produced concentration‐dependent contractions with an EC 50 value of approximately 10 n m . Contractile responses induced by SRIF were insensitive to atropine (1 μ m ) or naloxone (1 μ m ) but abolished by tetrodotoxin (1 μ m ). Somatostatin‐28 (SRIF 28 ), also induced concentration‐dependent contractions and was equipotent with SRIF. Phosphoramidon (1 μ m ) and amastatin (10 μ m ) did not increase the potency of either SRIF or SRIF 28 . 3 The SRIF peptide analogues, octreotide, SRIF 25 , seglitide, angiopeptin and CGP23996 (1 n m ‐1 μ m ) produced contractile responses in the rat distal colon, each having similar potency and maximal activity relative to SRIF. The SSTR 2 receptor‐selective hexapeptide, BIM23027 (0.1 n m ‐1 μ m ), and the SRIF stereoisomer, D‐Trp 8 ‐SRIF (0.1 n m ‐1 μ m ), were the most potent agonists examined being approximately 12 and 7 times more potent than SRIF, respectively. In contrast, the SSTR 5 receptor‐selective analogue, L362,855, was approximately 120 times weaker than SRIF, whilst the SSTR 3 receptor‐selective analogue, BIM23056, was inactive at concentrations up to 3 μ m . 4 The putative SRIF receptor antagonist, (cyclo(7‐aminoheptanoyl Phe‐D‐Trp‐Lys‐Thr[Bzl]))(CPP) (1 μ m ), had no agonist activity and had no effect on contractions induced by SRIF. 5 The contractile actions of BIM23027 and seglitide were subject to pronounced desensitization. Desensitization of preparations by BIM23027 (0.3 μ m ) abolished the contractile action of SRIF and SRIF 28 but had no effect on contractions produced by acetylcholine (0.1 n m ‐1 μ m ), suggesting that BIM23027, SRIF and SRIF 28 act via a common receptor mechanism. 6 In conclusion, the rat isolated distal colon contracts in response to SRIF and a number of SRIF analogues. Seglitide and octreotide exhibited similar potency and maximal activity relative to SRIF, suggesting that in the rat colon the receptor mediating contraction belongs to the SRIF 1 ‐receptor group, of which the recombinant SSTR 2 , SSTR 3 and SSTR 5 receptors appear to be subtypes. The high potency of BIM23027, the weak agonist activity of L362,855 and the lack of activity exhibited by BIM23056 suggests that the SRIF receptor mediating contraction in the rat distal colon is similar to the recombinant SSTR 2 receptor.