ライフサイエンスコーパス: SRIF

1 SRIF action was blocked in cells pretreated with pertuss

2 SRIF amacrine cells, DA amacrine cells, and M1 ipRGCs fo

3 SRIF analog affinities were determined by membrane radio

4 SRIF analogs with selective affinity for this receptor m

5 SRIF and SMS increased the phosphorylation of the 71-kDa

6 SRIF immunostaining was observed in widely spaced amacri

7 SRIF increases K(+) currents, decreases Ca(2+) currents,

8 SRIF modulation of the microcircuit was investigated wit

9 SRIF reduced Ca(2+) current in rods by 33% but increased

10 SRIF, at concentrations of 100-500 nM, enhanced a delaye

11 SRIF-immunoreactive cells have two to five primary proce

12 1,2,5)-[d-Trp(8),(N(alpha)Me)IAmp(9),Tyr(11)]SRIF (34), and Des-AA(1,2,5)-[d-Agl(8)(N(beta)Me,2-napht

13 gl(8)(N(beta)Me,2-naphthoyl),IAmp(9),Tyr(11)]SRIF (42) (Agl = aminoglycine) are sst(1) agonists in th

14 es-AA(1,2,5)-[DTrp(8),IAmp(9),(125)ITyr(11)]-SRIF ((125)I-25) and des-AA(1,2,5)-[DTrp(8),IAmp(9), (12

15 and des-AA(1,2,5)-[DTrp(8),IAmp(9),Tyr(11)]-SRIF (25) are about (1)/(7), (1)/(4), (1)/(125), and (1)

16 3)-[DAgl(NMe,2naphthoyl)(8),IAmp(9),Tyr(11)]-SRIF-NH(2) (27) in DMSO.

17 5)-[Tyr(2),Glu(7),d-Trp(8),IAmp(9),hhLys(12)]SRIF (31) (sst(1) IC(50) = 16 nM) and cyclo(7-12) Des-AA

18 lu(7),d-Trp(8),IAmp(9),m-I-Tyr(11),hhLys(12)]SRIF (45) (sst(1) IC(50) = 6.1 nM) had equal or improved

19 1,2,5)-[d-Trp(8),IAmp(9),(N(alpha)Me)Ser(13)]SRIF (19), Des-AA(1,2,5)-[d-Trp(8),IAmp(9),(N(alpha)Me)C

20 1,2,5)-[d-Trp(8),IAmp(9),(N(alpha)Me)Cys(14)]SRIF (20), Des-AA(1,2,5)-[d-Trp(8),(N(alpha)Me)IAmp(9),T

21 Trp(8)-Lys(9)-Thr(10)-Cys(11)]Thr(12)-NH(2) (SRIF numbering), at the five known human somatostatin re

22 ls and acute and chronic pain in humans; (3) SRIF inhibits dorsal horn neuronal activity; and (4) SRI

23 ibits dorsal horn neuronal activity; and (4) SRIF reduces responses of joint mechanoreceptors to noxi

24 wis et al. on the effects on K(i)s of Ala(6)-SRIF-14-amide at the five receptor subtargets.

25 e the synthesis of two analogues of D-Trp(8)-SRIF in which Phe(6) and Phe(11) were replaced by the pr

26 also found that pyrazinylalanine(7)-D-Trp(8)-SRIF-14 does not bind, suggesting a repulsive interactio

27 Des-AA(1,2,4,13)-[d-Trp(8)]SRIF (2) retained high binding affinity at all receptors

28 eptors but sst(1), Des-AA(1,2,4,5)-[d-Trp(8)]SRIF (3) at sst(4) and sst(5), and Des-AA(1,2,4,5,13)-[d

29 and sst(5), and Des-AA(1,2,4,5,13)-[d-Trp(8)]SRIF (4) at sst(2) and sst(4) (AA = amino acid).

30 Des-AA(1,2,4,12,13)-[d-Trp(8)]SRIF (6) was potent and sst(4)-selective (>25-fold); Des

31 ve (>25-fold); Des-AA(1,2,5,12,13)-[d-Trp(8)]SRIF (7) and Des-AA(1,2,4,5,12,13)-[d-Trp(8)]-SRIF (9, O

32 nalogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylala

33 RIF (7) and Des-AA(1,2,4,5,12,13)-[d-Trp(8)]-SRIF (9, ODT-8) were most potent at sst(4) and moderatel

34 Des-AA(1,2,5)-[d-Trp(8), (N(alpha)Me)IAmp(9)]SRIF (17), Des-AA(1,2,5)-[d-Trp(8),IAmp(9),(N(alpha)Me)S

35 ent compound Des-AA(1,2,5)-[d-Nal(8),IAmp(9)]SRIF (4).

36 Des-AA(1,2,5)-[d-Trp(8)/d-Nal(8),IAmp(9)]SRIF (AA = amino acid, Nal = 3-(2-naphthyl)-alanine, IAm

37 lective Des-AA(1,5)-[Tyr(2),d-Trp(8),IAmp(9)]SRIF, (14, sst(1) IC(50) = 14 nM) were prepared in which

38 o des-AA(1,5)-[(125)ITyr(2),DTrp(8),IAmp(9)]-SRIF ((125)I-16) for the detection of sst1 tumors in rec

39 7 to yield des-AA(1,2,5)-[D2Nal(8),IAmp(9)]-SRIF (13) and in 16 to yield des-AA(1,5)-[Tyr(2),D2Nal(8

40 yield des-AA(1,5)-[Tyr(2),D2Nal(8),IAmp(9)]-SRIF (17) was intended to increase chemical stability, s

41 (16), des-AA(1,2,5)-[Tyr(7),DTrp(8),IAmp(9)]-SRIF (23), and des-AA(1,2,5)-[DTrp(8),IAmp(9),Tyr(11)]-S

42 at des-AA(1,4,5,13)-[Tyr(2),DTrp(8),IAmp(9)]-SRIF (33) and des-AA(1,4,5,6,12,13)-[Tyr(2),DTrp(8),IAmp

43 s-AA(1,4,5,6,12,13)-[Tyr(2),DTrp(8),IAmp(9)]-SRIF (34) progressively lost affinity for all receptors.

44 ffinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys-Phe-Phe-DTrp-IAmp-Thr-Phe-Thr-Ser-Cys-

45 5) (7), des-AA(1,5)-[Tyr(2),DTrp(8),IAmp(9)]-SRIF (CH-288) (16), des-AA(1,2,5)-[Tyr(7),DTrp(8),IAmp(9

46 AA(1,4-6,10,12,13)-[DPhe(2),DTrp(8),IAmp(9)]-SRIF-Thr-NH(2) (16), des-AA(1,2,4-6,10,12,13)-[DAgl(NMe,

47 ,10,12,13)-[DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH(2) (23), and des-AA(1,2,4-6,10,12,13)-[DAgl(

48 3)-[DTyr(2),DAgl(NMe,2naphthoyl)(8),IAmp(9)]-SRIF-Thr-NH(2) (25) was radio-iodinated ((125)I-25) and

49 A SRIF-responsive yeast growth assay was used as a primary

50 h or without pretreatment with a long-acting SRIF agonist.

51 ess in vivo activity in the absence of added SRIF.

52 In addition, SRIF-immunoreactive cells often have a fine-caliber axon

53 nity of 75 nM and an IC50 of 15.1 nM against SRIF-14 in a rat in vitro antagonist bioassay.

54 tin receptor SSTR5) with its peptide agonist SRIF-14.

55 )]-Thr (15)-NH2 (1) (a somatostatin agonist, SRIF numbering) and H-Cpa (2)-c[DCys (3)-Tyr (7)-DTrp (8

56 RIF numbering) (ODT-8) that is potent at all SRIF receptor subtypes (sst's) but sst(1).

57 = 4-(N-isopropyl)-aminomethylphenylalanine, SRIF = somatostatin), with or without a tyrosine or mono

58 Here, an SRIF antagonist with no detectable agonist activity has

59 t modify the GH rise after termination of an SRIF infusion.

60 eatment of hepatocytes incubated with GH and SRIF, or with GH and octreotide, abrogated the inhibitor

61 0.09 nM) than Lanreotide (EC50, 2.30 nM) and SRIF (EC50, 0.19 nM).

62 RIF) receptors (SSTRs) 1 and 2 bind SRIF and SRIF 28 with high affinity, although a number of synthet

63 The SARs of the glycosides at SRIF receptors differ markedly from those at the NK-1 re

64 statin (SRIF) receptors (SSTRs) 1 and 2 bind SRIF and SRIF 28 with high affinity, although a number o

65 nity constant (Ki) of 172 +/- 12 nM, blocked SRIF inhibition of adenylate cyclase in vitro (IC50 = 5.

66 Both SRIF and its receptors were subsequently found widely di

67 This D-hexapeptide bound SRIF receptor type 2 with an affinity constant (Ki) of 1

68 act the disinhibition of M1 ipRGCs caused by SRIF inhibition of DA amacrine cells.

69 ransfected cells was completely displaced by SRIF-28 or the sst(4)-selective L-803,087.

70 rods and cones were differently modulated by SRIF.

71 (1,2,5)-[DTrp(8),IAmp(9), (125)ITyr(11)]-Cbm-SRIF ((125)I-27), used them as in vitro tracers, and fou

72 des-AA(1,2,5)-[DTrp(8),IAmp(9),Tyr(11)]-Cbm-SRIF (27) and des-AA(1,2,5)-[DCys(3),DTrp(8),IAmp(9),Tyr

73 des-AA(1,2,5)-[DTrp(8),IAmp(9),Tyr(11)]-Cbm-SRIF (27) increased affinity slightly as well as improve

74 1,2,5)-[DCys(3),DTrp(8),IAmp(9),Tyr(11)]-Cbm-SRIF (29) show agonistic activity in a cAMP assay; there

75 eraction of M1 ipRGCs and DA amacrine cells, SRIF amacrine cells would provide inhibitory modulation

76 is important for the selectivity of certain SRIF agonists for binding to SSTR1.

77 ere used to confirm and further characterize SRIF antagonist activity.

78 In conclusion, cytotoxic SRIF analogue AN-238 inhibits the growth of experimental

79 nomas, the treatment with targeted cytotoxic SRIF analogue AN-238, consisting of 2-pyrrolinodoxorubic

80 Dicyclic SRIF agonists of the sst(1)-selective Des-AA(1,5)-[Tyr(2

81 Recently, five pharmacologically different SRIF receptors (sst1-5) were cloned.

82 when c-SOM is coapplied with three different SRIF agonists.

83 Replacement of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/-47 to 2

84 A 30-min exposure of cells to either SRIF or the analog SMS 201-995 (SMS) reduced both the po

85 ifficult to establish the role of endogenous SRIF release in the absence of pure SRIF antagonists.

86 n-14 somatotropin-release inhibiting factor (SRIF) and 2 of its analogs, (125)I-WOC 4a and (111)In-pe

87 tin [somatotropin release inhibiting factor (SRIF)] also inhibits the intrinsic light response of M1

88 tin [somatotropin release-inhibiting factor (SRIF)] is widely distributed in the body and exerts a va

89 [or somatotropin release-inhibiting factor (SRIF)] receptors, sst(2A), and studied the modulatory ac

90 in (somatotrophin release-inhibiting factor, SRIF) were determined in cultured locus coeruleus neuron

91 ary (somatotropin release inhibitory factor, SRIF).

92 ter the functional expression of human fetal SRIF neurons in culture and if so, is this effect fetal-

93 on of smoking-related interstitial fibrosis (SRIF) is relatively recent, with differentiated histolog

94 xis, providing a mechanistic explanation for SRIF analog action in treating patients with GH-secretin

95 mple a 4-benzyl substituent is important for SRIF receptor binding, but the 4-desbenzyl analogue 27 w

96 rings to bind the Trp(8) binding pocket for SRIF-14 and the inability of pyrazine to do so was expla

97 of sst mRNAs suggests a significant role for SRIF in the regulation of GI function.

98 During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose

99 a-turn such as the potent cyclic hexapeptide SRIF agonist L-363,301 (6a), but not substance P.

100 ng receptor autoradiography; those with high SRIF receptor subtype 1 (sst(1)) affinity and selectivit

101 In a proportion of patients, however, SRIF analogs may lead to discordant growth hormone (GH)

102 of a glucose-based peptidomimetic at a human SRIF receptor to date (K(i) 53 +/- 23 nM, n = 6 at sst4)

103 atostatin (SRIF) analogues at the five human SRIF receptors (sst) was determined to identify sterical

104 lubility and enhanced affinity for the human SRIF subtype receptor 4 (sst4).

105 1)/(1000) that of 1 to the other three human SRIF receptor subtypes.

106 potent and highly selective binding to human SRIF subtype 1 receptors (sst(1)).

107 potent and highly selective binding to human SRIF type 2 (sst2) receptors.

108 potent and highly selective binding to human SRIF type 4 (sst(4)) receptors.

109 r from GHRH release or from acute decline in SRIF secretion.

110 We first tested whether an acute decline in SRIF, independent of GHRH action, would release GH.

111 BDNF alone led to a significant increase in SRIF production (p=0.014), whereas exposure to gp120 alo

112 After 24-h incubation, SRIF was degraded or recycled, whereas its protease-resi

113 and gp120 led to an increase in BDNF-induced SRIF production which was significantly greater than tha

114 with 100 nm SRIF for 30 min reduced maximal SRIF inhibition of adenylyl cyclase from 40 to 10%.

115 or internalization, the mechanisms mediating SRIF receptor (sst) desensitization are unknown.

116 One hundred nanomolar SRIF-28 activated an inwardly rectifying K+ current (ISR

117 e numbering refers to the position in native SRIF), with Xxx(7) being Phe/Ala/Tyr, Yyy(8) being Trp/D

118 e numbering refers to the position in native SRIF), with Xxx7 being Ala/Aph, exhibit potent and highl

119 brane, they also potentiate the neuropeptide SRIF inhibitory effects on seizure activity.

120 Treatment of cells with 100 nm SRIF for 30 min reduced maximal SRIF inhibition of adeny

121 In cell-attached patches, 100 nM SRIF-14 activated two types of single-channel currents w

122 The activation of ISRIF by 100 nM SRIF-28 was, however, inhibited 93 % by BIM-23056; CYN-1

123 pported these results by showing that 500 nM SRIF reduced a K(+)-induced increase in intracellular Ca

124 s do not stain for GAD-67, parvalbumin, NPY, SRIF, or NOS.

125 nodoxorubicin (AN-201) linked to octapeptide SRIF carrier RC-121, may overcome this resistance by pro

126 ic binding pocket such as that for Trp(8) of SRIF-14.

127 st(2A), and studied the modulatory action of SRIF on voltage-gated K(+) and Ca(2+) currents in rod an

128 These parallel actions of SRIF may serve to counteract the disinhibition of M1 ipR

129 This allows the actions of SRIF on DA amacrine cells to proceed with adjusting reti

130 orsal root ganglion cells; (2) activation of SRIF receptors results in inhibition of both nociceptive

131 hetic hexapeptide and octapeptide analogs of SRIF bind selectively to SSTR2.

132 (11) stabilize the bioactive conformation of SRIF-14.

133 rs are under the tonic inhibitory control of SRIF.

134 Furthermore, the sparse distribution of SRIF-immunoreactive somata, the wide-ranging, asymmetric

135 The inhibitory effect of SRIF was not apparent without added GH and in the presen

136 The effects of SRIF-14 were mimicked by 100 nM L-362,855 (a partial ago

137 onal significance of transient expression of SRIF and its receptors in the development of the cerebel

138 lling pathway(s) mediating BDNF induction of SRIF production; an effect expressed by fetal brains thr

139 Furthermore, intraplantar injection of SRIF antiserum also results in nociceptive behaviors.

140 In addition, the number of SRIF-immunoreactive somata remains unchanged following t

141 NF or BDNF+gp120; BDNF induced production of SRIF during the subsequent 24-48 h was assessed.

142 dy of the structure-activity relationship of SRIF.

143 dy of the structure-activity relationship of SRIF.

144 H3 cells demonstrate that basal secretion of SRIF-related material is largely calcium-dependent and t

145 (7), (1)/(4), (1)/(125), and (1)/(4) that of SRIF-28 (1) to sst1, respectively, about (1)/(65), (1)/(

146 gands at the hSSTRs is compared with that of SRIF.

147 -DTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) by one of the four conformationa

148 -dTrp(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)]-OH (SRIF numbering) (ODT-8) that is potent at all SRIF recep

149 oid receptor antagonism influence peripheral SRIF effects on nociceptors.

150 ium is absolutely required for efficient pro-SRIF cleavage, even at the optimal pH of 6.1.

151 3187 to determine the role of calcium in pro-SRIF cleavage and nascent vesicle formation from the tra

152 ry GH3 cells expressing prosomatostatin (pro-SRIF) to study prohormone processing and nascent secreto

153 Here we demonstrate that pro-SRIF cleavage was markedly inhibited when lumenal free c

154 her, these observations demonstrate that pro-SRIF processing and budding of nascent secretory vesicle

155 ative fashion to identify AC-178,335, a pure SRIF antagonist of the sequence Ac-hfirwf-NH2.

156 dogenous SRIF release in the absence of pure SRIF antagonists.

157 show that prolonged exposure to radiolabeled SRIF analogs significantly increases their cellular inte

158 ors, the SRIF receptors (SSTR 1-5) recognize SRIF and related peptides which retain its beta-turn suc

159 In the rabbit retina, SRIF immunoreactivity is present in a sparse population

160 as shown to be the case in 18-membered ring SRIF octapeptides.

161 Although several SRIF antagonists have recently been described, none have

162 Somatostatin (SRIF) analogs provide safe and effective therapy for acr

163 Somatostatin (SRIF) is a neuroactive peptide that is distributed throu

164 Somatostatin (SRIF) is the main inhibitory peptide regulating growth h

165 Somatostatin (SRIF), a hypothalamic inhibitor of pituitary growth horm

166 Because somatostatin (SRIF) receptors (ssts) are present in colorectal carcino

167 7) and irreversibly reduced by somatostatin (SRIF-14); this was associated with hyperpolarization of

168 inding affinity of short chain somatostatin (SRIF) analogues at the five human SRIF receptors (sst) w

169 inity (IC(50) = 2-4 nM) cyclic somatostatin (SRIF) octapeptides.

170 binding properties to all five somatostatin (SRIF) receptors using receptor autoradiography; those wi

171 that structural constraints in somatostatin (SRIF) analogues may result in receptor selectivity, and

172 hin the hippocampus, the major somatostatin (SRIF) receptor subtype, the sst2A receptor, is localized

173 albumin, neuropeptide Y (NPY), somatostatin (SRIF), or nitric oxide synthase (NOS).

174 structures of six analogues of somatostatin (SRIF) are described.

175 yclic octapeptide analogues of somatostatin (SRIF) are described.

176 Changes in the expression of somatostatin (SRIF) have been observed in the brains of HIV encephalit

177 eleasing hormone (GHRH) and of somatostatin (SRIF) in pharmacologically stimulated growth hormone (GH

178 tapeptide agonist analogues of somatostatin (SRIF) in the free form are described.

179 endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy

180 rch for synthetic analogues of somatostatin (SRIF) which exhibit selective affinities for the five kn

181 synthetic peptide analogues of somatostatin (SRIF) which exhibit selective affinities for the five kn

182 s a major source and target of somatostatin (SRIF).

183 opments, unusual properties of somatostatin (SRIF, 1) analogues are still being uncovered.

184 ucose-based peptidomimetics of somatostatin (SRIF-14), we sought to improve the water solubility of o

185 re required for the binding of somatostatin (SRIF-14).

186 ness to the inhibitory peptide somatostatin (SRIF) or its clinically used analogs can desensitize wit

187 The endogenous peptides somatostatin (SRIF) and substance P comprise very different structures

188 The sst1 somatostatin (SRIF) receptor subtype is widely expressed in the endocr

189 The somatostatin (SRIF) receptors (SSTRs) 1 and 2 bind SRIF and SRIF 28 wi

190 We therefore tested SSTR subtype-specific SRIF analogs in primary human fetal pituitary cultures (

191 The results demonstrate that SRIF acts both centrally and peripherally to control the

192 These findings demonstrate that SRIF receptors maintain a tonic inhibitory control over

193 Several lines of evidence indicate that SRIF is important in nociceptive processing: (1) it is l

194 Taken together, these data indicate that SRIF-immunoreactive neurons of the rabbit retina are dis

195 Our results suggest that SRIF may play a role in the regulation of glutamate tran

196 The SRIF-induced activation of the inward rectifier was supp

197 he nature of the ligand binding sites at the SRIF receptor.

198 to synthesize peptidomimetics that bind the SRIF receptors on AtT-20 mouse pituitary cells, five clo

199 In AtT-20 cells, the SRIF-induced activation of inward rectifier K+ currents

200 DA amacrine cells and M1 ipRGCs express the SRIF receptor subtypes sst(2A) and sst4 respectively.

201 above results indicate that Gi mediates the SRIF effects on inward rectifier K+ currents.

202 In locus coeruleus neurones, the SRIF-induced activation of inward rectifier K+ currents

203 endent manner, intraplantar injection of the SRIF receptor antagonist cyclo-somatostatin (c-SOM) resu

204 h both bind G-protein-coupled receptors, the SRIF receptors (SSTR 1-5) recognize SRIF and related pep

205 a i3 antibody injection, suggesting that the SRIF response is mediated through G alpha i1 and/or G al

206 suggest that G alpha i2 is involved in this SRIF response.

207 d this increase is blocked by the same three SRIF agonists.

208 Thus, SRIF regulation of GH and TSH in primary human fetal pit

209 HEK 293 cells (sst2)] utilizing [125I]Tyr11-SRIF as the radioligand.

210 wth hormone in vitro antagonist assay versus SRIF (1 nM).

211 d by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA).

212 To elucidate whether SRIF acts peripherally on the GH-IGF-I axis, we showed t

213 Incubation of cells with SRIF also caused a rapid (t(12) < 2 min) increase in sst

214 irment of Mch-induced vasodilation seen with SRIF alone.

215 Treatment with SRIF and GH increased protein tyrosine phosphatase (PTP)