Anxiogenic effects of the CCK(B) agonist pentagastrin in humans and dose-dependent increase in plasma C-peptide levels.

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Radu D, Ahlin A, Svanborg P, Lindefors N

Anxiogenic effects of the CCK(B) agonist pentagastrin in humans and dose-dependent increase in plasma C-peptide levels.

Psychopharmacology (Berl). 2002 Jun;161(4):396-403. Epub 2002 Apr 17.

PubMed ID

12073167 [ View in PubMed

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Abstract

RATIONALE: Cholecystokinin type B (CCK(B)) receptor agonists such as pentagastrin or CCK-4 have panic-like anxiogenic effects in humans. It has also been shown that CCK-4 can stimulate insulin release and thus C-peptide release from pancreatic islet cells. Combined, these mechanisms may provide a basis for a bioassay. OBJECTIVES: Our aim was to study if a pentagastrin bolus injection evokes insulin release (as measured by C-peptide) and if the levels of C-peptide correlate to the anxiogenic effect of pentagastrin. METHODS: Pentagastrin was given in bolus IV injections to healthy volunteers at increasing doses (0.003, 0.012, 0.05 and 0.2 microg/kg). RESULTS: A significant increase in the plasma level of C-peptide was observed 2-4 min after the highest dose of pentagastrin. This increase was accompanied by a transient panic-like anxiety within 2 min following pentagastrin, measured using a state anxiety scale. Also, 0.05 microg/kg pentagastrin gave a minor but significant subjective discomfort at the same time interval. The basal plasma level of C-peptide preceding the pentagastrin injection showed a positive correlation to the intensity of the subsequent pentagastrin-induced panic-like anxiety as rated on the state anxiety scale. In addition, basal plasma levels of cortisol were positively correlated to the subsequent pentagastrin-induced increase in plasma C-peptide levels. CONCLUSIONS: Our results imply a possible relationship between insulin/C-peptide release and sensitivity to psychotropic activation by CCK(B) receptor stimulation. Furthermore, we postulate that both basal and pentagastrin-induced plasma levels of C-peptide may possess characteristic phenotype properties for anxiety related traits.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pentagastrin	Gastrin/cholecystokinin type B receptor	Protein	Humans	Yes	Agonist	Details