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CCK-4 Acetate

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CAT#
10-101-74
Synonyms/Alias
CCK-4; CCK4; CCK 4; Gastrin Tetrapeptide; Cholecystokinin Octapeptide (5-8); Cholecystokinin Tetrapeptide; Gastrin (14-17) (human)
CAS No.
35144-91-3
Sequence
H-Trp-Met-Asp-Phe-NH2 acetate
M.W/Mr.
596.71
Molecular Formula
C29H36N6O6S
Source
Synthetic
Long-term Storage Conditions
−20°C
Application
CCK-4 acts primarily in the brain as an anxiogenic. It is commonly used in scientific research to induce panic attacks for the purpose of testing new anxiolytic drugs.
Description
Cholecystokinin tetrapeptide (CCK-4, also PTK7) is a peptide fragment derived from the larger peptide hormone cholecystokinin. CCK-4 acts primarily in the brain as an anxiogenic, although it does retain some GI effects, but not as much as CCK-8 or the full length polypeptide CCK-58.
Areas of Interest
Diseases
  • Background
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  • References

CCK-4 has potent anxiogenic properties both in patients with panic disorder and in healthy volunteers. Recent data suggest that CCK-4-induced panic is attenuated by antipanic treatment. A decrease of the anxiogenic effects of CCK-4 has been shown after treatment with benzodiazepines in healthy volunteers. Moreover, antidepressants that are commonly used as antipanic treatment, e.g. imipramine, fluvoxamine and citalopram reduced CCK-4-induced panic in patients with panic disorder.

CAS: 133099-04-4 (net), 133099-07-7 (hydrobromide)
Sequence: ---
M.W: 505.44606
Molecular Formula: C28H29BrN2O2
CAS: 201530-41-8
Sequence: ---
M.W: 373.3615
Molecular Formula: C21H15N3O4
CAS: 60731-46-6 (net)
Sequence: Cyclo(-Ser-Asn-Leu-Ser-Thr-Asu)-Val-Leu-Gly-Lys-Leu-Ser-Gln-Glu-Leu-His-Lys-Leu-Gln-Thr-Tyr-Pro-Arg-Thr-Asp-Val-Gly-Ala-Gly-Thr-Pro-NH2 acetate salt
M.W: 3363.8
Molecular Formula: C148H244N42O47
CAS: 17035-90-4 (net), 53308-83-1 (acetate)
Sequence: H-Arg(Me)-OH acetate salt
M.W: 248.28
Molecular Formula: C9H20N4O4
CAS: 163913-87-9
Sequence: Met-Glu-Val-Gly-Trp-Tyr-Arg-Ser-Pro-Phe-Ser-Arg-Val-Val-His-Leu -Tyr-Arg-Asn-Gly-Lys
M.W: 2581.99
Molecular Formula: C118H177N35O29S

Experimental panic induction with cholecystokinin tetrapeptide (CCK-4) is considered as a suitable model to investigate the pathophysiology of panic attacks. While only a few studies investigated the brain activation patterns following CCK-4, no data are available on the putative involvement of the amygdala in the CCK-4 elicited anxiety response. We studied the functional correlates of CCK-4-induced anxiety in healthy volunteers by means of functional magnetic resonance imaging (fMRI) and region of interest (ROI) analysis of the amygdala. Sixteen healthy volunteers underwent challenge with CCK-4 compared with placebo in a single-blind design. Functional brain activation patterns were determined for the CCK-4-challenge, the placebo response and anticipatory anxiety (AA). CCK-4-induced anxiety was accompanied by a strong and robust activation (random effects analysis, P < 0.00001, uncorrected for multiple testing) in the ventral anterior cingulate cortex (ACC), middle and superior frontal gyrus, precuneus, middle and superior temporal gyrus, occipital lobe, sublobar areas, cerebellum, and brainstem. In contrast, random effects group analysis for placebo and AA using the same level of significance generated no significant results. Using a more liberal level of significance, activations could be observed in some brain regions such as the dorsal part of the ACC during AA (random effects analysis, P < 0.005). Overall functional responses did not differ between panickers and nonpanickers. Only 5 of 11 subjects showed strong amygdala activation. However, ROI analysis pointed towards higher scores in fear items in these subjects. In conclusion, while overall brain activation patterns are not related to the subjective anxiety response to CCK-4, amygdala activation may be involved in the subjective perception of CCK-4-induced fear.

Eser, D., Leicht, G., Lutz, J., Wenninger, S., Kirsch, V., Schüle, C., ... & Rupprecht, R. (2009). Functional neuroanatomy of CCK‐4‐induced panic attacks in healthy volunteers. Human brain mapping, 30(2), 511-522.

3alpha-reduced neuroactive steroids such as 3alpha, 5alpha-tetrahydroprogesterone (3alpha, 5alpha-THP) and 3alpha, 5alpha-tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3alpha, 5alpha-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3alpha, 5alpha-THDOC concentrations during experimental panic induction. Therefore, we quantified 3alpha, 5alpha-THDOC concentrations in 10 healthy volunteers (nine men, one woman) before and after panic induction with CCK-4 by means of a highly sensitive and specific gas chromatography/mass spectrometry analysis. CCK-4 elicited a strong panic response as assessed by the Acute Panic Inventory. This was accompanied by an increase in 3alpha, 5alpha-THDOC, ACTH and cortisol concentrations. This increase in 3alpha, 5alpha-THDOC might be a consequence of hypothalamic-pituitary-adrenal (HPA) axis activation following CCK-4-induced panic, and might contribute to the termination of the anxiety/stress response following challenge with CCK-4 through enhancement of GABAA receptor function.

Eser, D., Di Michele, F., Zwanzger, P., Pasini, A., Baghai, T. C., Schüle, C., ... & Romeo, E. (2005). Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3 [alpha], 5 [alpha] tetrahydrodeoxycorticosterone (3 [alpha], 5 [alpha]-THDOC) in healthy volunteers. Neuropsychopharmacology, 30(1), 192.

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