Gastrin-1, human primarily acts on CCK₂ receptors (also referred to as CCK_B receptors), exhibiting low affinity for CCK₁ receptors. The study demonstrates that the stimulant actions of Gastrin-1, human on both pepsinogen and acid secretion are insensitive to the CCK₁ receptor antagonist devazepide but are fully prevented by the CCK₂ receptor antagonist L-365,260. [2]

The stomach produces the endogenous peptide known as gastrin I, which works by absorbing cholecystokinin 2 (CCK2) [1].

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Human Gastrin I increases stomach burden and acid sovereignty when administered intravenously at doses of 1.5, 5, 15, and 45 nmol/kg [1].

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In anaesthetized rats with perfused gastric lumen, intravenous (i.v.) bolus injection of Gastrin-1, human at doses of 1.5, 5, 15, and 45 nmol/kg caused a dose-dependent increase in both pepsinogen and acid secretion, with maximal effect observed at 15 nmol/kg. At this dose, Gastrin-1, human increased pepsinogen output to a peak value of 252.7 ± 27.1 μg pepsin/15 min (n=10) and acid output to 34.4 ± 3.8 μeq H⁺/15 min. Compared to CCK-8S, Gastrin-1, human induced a significantly lower pepsinogen response (P<0.001) but a significantly higher acid hypersecretion (P<0.01). [2]
Pretreatment with the CCK₁ receptor antagonist devazepide (1.25 and 2.5 μmol/kg i.v.) did not modify the stimulant actions of Gastrin-1, human (15 nmol/kg) on pepsinogen or acid secretion. However, the CCK₂ receptor antagonist L-365,260 (2.5 and 5 μmol/kg i.v.) completely prevented both the pepsinogen and acid secretory effects of Gastrin-1, human. Combined administration of devazepide (2.5 μmol/kg) and L-365,260 (5 μmol/kg) also abolished these responses. [2]
Bilateral cervical vagotomy or pretreatment with atropine (1 μmol/kg i.v.) did not significantly modify the effects of Gastrin-1, human (15 nmol/kg) on pepsinogen or acid secretion. Cimetidine (10 μmol/kg i.v.) partly prevented the acid stimulant effect of Gastrin-1, human (-64.6%) without affecting its pepsigogue action. Pretreatment with α-fluoromethylhistidine (450 μmol/kg i.p. twice daily for 2 days) produced similar results: acid secretion was reduced but pepsinogen response remained unchanged. [2]
In animals pretreated with omeprazole (90 μmol/kg i.v.) to block gastric acid secretion, Gastrin-1, human (15 nmol/kg) failed to stimulate acid output but still significantly increased pepsinogen secretion. Under omeprazole pretreatment, the pepsigogue action of Gastrin-1, human was insensitive to devazepide but was prevented by L-365,260. [2]
Functional ablation of capsaicin-sensitive sensory neurons by systemic capsaicin pretreatment (125 mg/kg s.c.) did not modify the excitatory effects of Gastrin-1, human (15 nmol/kg) on pepsinogen or acid secretion. Similarly, topical intragastric application of lidocaine (4% for 15 min) to induce surface anaesthesia of the gastric mucosa failed to alter these responses. [2]
Blockade of the nitric oxide (NO) synthase pathway by systemic administration of L-NAME (75 μmol/kg i.v.) prevented the stimulant action of Gastrin-1, human (15 nmol/kg) on pepsinogen secretion (-71.7%), without affecting the concomitant increase in acid output. Pretreatment with L-arginine (2 mmol/kg i.v.), but not D-arginine (2 mmol/kg i.v.), completely restored the pepsigogue effect of Gastrin-1, human. [2]
Gastrin-1, human (15 nmol/kg i.v.) significantly increased the gastric luminal release of NO breakdown products (NOₓ) from a basal value of 12.3 ± 1.7 nmol/30 min. This stimulant effect was abolished by pretreatment with L-NAME (75 μmol/kg i.v.). [2]

Male Wistar rats weighing 200-220 g were used. Animals were fasted for 24 hours before experiments but had free access to water. Anaesthesia was induced with urethane (1.2 g/kg i.p.). The trachea was cannulated to maintain airway patency. A polyethylene catheter was introduced into the oesophagus and advanced 5 mm beyond the gastroesophageal junction. After midline laparotomy, a catheter was inserted into the duodenum and advanced 5 mm beyond the pylorus. The stomach lumen was continuously perfused with saline solution (154 mM NaCl, pH 7.0 ± 0.2) at 1 ml/min and 37°C. Fifteen-minute effluent fractions were collected for pepsinogen and acid measurement. After surgical preparation, basal gastric secretion was allowed to stabilize for 30 min, followed by two consecutive 15-min collections for basal values. Then, secretions were monitored at 15-min intervals for an additional 120 min. Gastrin-1, human was administered as an i.v. bolus immediately after collection of basal effluent samples, at doses of 1.5, 5, 15, and 45 nmol/kg. For antagonist studies, animals were pretreated i.v. with atropine (1 μmol/kg), cimetidine (10 μmol/kg), devazepide (1.25-2.5 μmol/kg), or L-365,260 (2.5-5 μmol/kg) 10 min before the end of the second basal effluent collection. α-Fluoromethylhistidine (450 μmol/kg i.p.) was given twice daily for two consecutive days. Omeprazole (90 μmol/kg i.v.) was administered 90 min before basal collection. Capsaicin pretreatment: 125 mg/kg s.c. given in four injections over two days (first day: 25 mg/kg morning and 25 mg/kg late afternoon; second day: 25 mg/kg morning and 50 mg/kg late afternoon), under ether anaesthesia with atropine, terbutaline, and aminophylline to counteract respiratory impairment. Lidocaine was applied topically by filling the gastric lumen with 3 ml of 4% lidocaine for 15 min, then rinsing. L-NAME (75 μmol/kg i.v.) was given 10 min before peptide administration, with or without L-arginine or D-arginine (2 mmol/kg i.v.) administered 15 min before L-NAME. [2]

[1]. International Union of Pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors. Pharmacol Rev. 1999 Dec;51(4):745-81.

[2]. CCK1 and CCK2 receptors regulate gastric pepsinogen secretion. Eur J Pharmacol. 1999 May 28;373(1):71-84.

Gastrin-17 is one of the major forms of gastrin. It is a peptide composed of 17 amino acid residues, namely Glp, Gly, Pro, Trp, Leu, Glu, Glu, Glu, Glu, Ala, Tyr, Gly, Trp, Met, Asp, and Phe-NH2. It possesses antitumor activity.

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Gastrin-1, human exerts its pepsigogue effects via activation of CCK₂ receptors on gastric chief cells, while CCK₁ receptors are not involved. The stimulant action on pepsinogen secretion is independent of gastric acidity, as demonstrated by experiments with omeprazole and intraluminal acid perfusion (pH 4 to 1) which did not alter the response. Endogenous cholinergic pathways (vagus nerve, atropine-sensitive muscarinic receptors) and histamine (via H₂ receptors or histidine decarboxylase) do not mediate the pepsinogen response to Gastrin-1, human. Somatostatin-14 infusion (15 nmol/kg/h i.v.) did not modify the pepsigogue effect. Capsaicin-sensitive sensory nerves and local afferent fibers (lidocaine-sensitive) are not involved. Instead, the NO pathway plays a significant role: Gastrin-1, human increases gastric NO synthase activity, leading to NO generation, which in turn stimulates pepsinogen secretion. This is supported by the inhibitory effect of L-NAME and its reversal by L-arginine, as well as the increased luminal NOₓ release. Pathophysiologically, conditions associated with hypergastrinemia (e.g., Helicobacter pylori-related gastritis, peptic ulcer) could maintain high rates of pepsinogen secretion independently of acid changes. The study also notes that gastrin receptor antagonists (e.g., L-365,260) may have therapeutic potential in peptic ulcer disease by blocking both acid and pepsinogen hypersecretion. [2]

C97H124N20O31S

2098.2029

2096.846

10047-33-3

16162108

White to off-white solid powder

1.4±0.1 g/cm3

2401.4±65.0 °C at 760 mmHg

1406.1±34.3 °C

0.0±0.3 mmHg at 25°C

1.624

-1.1

26

32

62

149

4730

15

C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)NCC(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC4=CC=CC=C4)C(=O)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@@H]7CCCN7C(=O)CNC(=O)[C@@H]8CCC(=O)N8

GKDWRERMBNGKCZ-RNXBIMIWSA-N

InChI=1S/C97H124N20O31S/c1-49(2)39-68(114-95(146)71(43-54-46-100-59-18-11-9-16-57(54)59)116-97(148)73-19-12-37-117(73)76(121)48-102-85(136)60-24-30-74(119)104-60)93(144)110-65(29-35-81(130)131)91(142)109-64(28-34-80(128)129)90(141)108-63(27-33-79(126)127)89(140)107-62(26-32-78(124)125)88(139)106-61(25-31-77(122)123)87(138)103-50(3)84(135)113-69(41-52-20-22-55(118)23-21-52)86(137)101-47-75(120)105-70(42-53-45-99-58-17-10-8-15-56(53)58)94(145)111-66(36-38-149-4)92(143)115-72(44-82(132)133)96(147)112-67(83(98)134)40-51-13-6-5-7-14-51/h5-11,13-18,20-23,45-46,49-50,60-73,99-100,118H,12,19,24-44,47-48H2,1-4H3,(H2,98,134)(H,101,137)(H,102,136)(H,103,138)(H,104,119)(H,105,120)(H,106,139)(H,107,140)(H,108,141)(H,109,142)(H,110,144)(H,111,145)(H,112,147)(H,113,135)(H,114,146)(H,115,143)(H,116,148)(H,122,123)(H,124,125)(H,126,127)(H,128,129)(H,130,131)(H,132,133)/t50-,60-,61-,62-,63-,64-,65-,66-,67-,68-,69-,70-,71-,72-,73-/m0/s1

(4S)-5-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-[[(2S)-4-carboxy-2-[[(2S)-4-carboxy-2-[[(2S)-4-carboxy-2-[[(2S)-4-carboxy-2-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[[(2S)-1-[2-[[(2S)-5-oxopyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]butanoyl]amino]-5-oxopentanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~23.83 mM)
NH4OH : 50 mg/mL (~23.83 mM)

Solubility in Formulation 1: 2.5 mg/mL (1.19 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (1.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)