CCK-4

Tetragastrin (Cholecystokinin tetrapeptide; CCK-4) is the C-terminal tetrapeptide of gastrin. Tetragastrin can stimulate gastric secretion[1]. Tetragastrin is a Cholecystokinin (CCK-4) receptor agonist[2]. Gastric mucosal protection[3].

Signaling Pathways >> GPCR/G Protein >> Cholecystokinin Receptor

Research Areas >> Metabolic Disease

The antagonist of histamine H2-receptors, Cimetidine inhibits the stimulatory effect of histamine in vitro and activates Tetragastrin stimulation of the adenylate cyclase activity. Tetragastrin and histamine activate adenylate cyclase of the rat gastric mucosa via different receptors[4].

In inbred Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine, Tetragastrin (s.c.; 1 mg/kg; every other day) treatment significantly reduces the incidence and the number of adenocarcinomas, and has a significantly lower labelling index of the antral mucosa[1]. Tetragastrin has potential for enhancing gastric mucosal protection associated with mucus secretion and/or mucus synthesis on the surface mucosa of rat gastric mucosa. A significant increase in the mucin content was noted in the mucus gel and surface mucosal layer. An increase in mucin in the mucus gel and surface mucosa would thus appear due to the administration of Tetragastrin[3]. Animal Model: Seven-week-old male Wistar rats, each weighing approximately 160 g[3] Dosage: 12, 120, or 400 μg/kg Administration: Administered subcutaneously (s.c.); followed by 50% ethanol-induced gastric injury Result: Caused a significant increase in mucin content in the corpus mucosa and prevented 50% ethanol-induced gastric mucosal damage in a dose-dependent manner.

[1]. M Tatsuta, et al. Effect of 6-hydroxydopamine on gastric carcinogenesis and tetragastrin inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Cancer Res. 1989 Aug 1;49(15):4199-203.

[2]. Nathalie Lara, et al. Pulmonary and systemic nitric oxide measurements during CCK-5-induced panic attacks. Neuropsychopharmacology. 2003 Oct;28(10):1840-5.

[3]. Y Komuro,et al. Effects of tetragastrin on mucus glycoprotein in rat gastric mucosal protection. Gastroenterol Jpn. 1992 Oct;27(5):597-603.

[4]. A A Karelin,et al. Tetragastrin activation of rat gastric mucosa adenyl cyclase in vitro. Biull Eksp Biol Med. 1981 Apr;91(4):440-1.

MOLECULAR FORMULA :

C37-H42-N6-O8-S

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,816,1995

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,816,1995

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 3,121,1969

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 3,121,1969

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 3,121,1969

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>100 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 3,121,1969

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 3,121,1969 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

46800 mg/kg/26W-I

TOXIC EFFECTS :

Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 3,121,1969