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


OBJECTIVE
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.
Radu
Diana
D
Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet Stockholm, 171 76 Stockholm, Sweden, diana.radu@ks.se
Ahlin
Arne
A
Svanborg
Pär
P
Lindefors
Nils
N
D000328:Adult; D000704:Analysis of Variance; D001007:Anxiety / Q000097:blood* / Q000139:chemically induced* / Q000523:psychology; D002096:C-Peptide / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010418:Pentagastrin / Q000009:adverse effects*; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000502:physiology; D018709:Statistics, Nonparametric
D002096:C-Peptide; D011949:Receptors, Cholecystokinin; D010418:Pentagastrin