Dose response of adrenocorticotropin and cortisol to the CCK-B agonist pentagastrin.
Cholecystokinin (CCK) is an abundant neurotransmitter in brain. Its functional significance in humans is incompletely understood, but it may modulate activity in the hypothalamic-pituitary-adrenal (HPA) axis. To explore this hypothesis, we examined the effects of varying doses (0 to 0.8 microgram/kg) of the CCK-B agonist pentagastrin on adrenocorticotropin (ACTH) and cortisol release in healthy human subjects. We also examined anxiety, heart rate (HR), and blood pressure (BP) responses. Pentagastrin induced large (up to 520% increase over baseline), significant and very rapid, dose-dependent elevations in ACTH and cortisol levels. Significant elevations in HR and BP were seen at all doses, without clear dose-response relationships. Anxious distress and symptom responses were also somewhat dose dependent; but hormonal responses were more robustly linked to pentagastrin dose than to these subjective measures. The HPA axis response to the CCK-B agonist pentagastrin may be a direct pharmacological effect. Further work is needed to determine the mechanisms and the physiological significance of CCK-mediated modulation of the human neuroendocrine stress axis.
Abelson
J L
JL
University of Michigan, Department of Psychiatry, Ann Arbor, USA.
Liberzon
I
I
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D001007:Anxiety / Q000139:chemically induced; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002766:Cholecystokinin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000139:chemically induced; D010418:Pentagastrin / Q000009:adverse effects / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists*; D012044:Regression Analysis
D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D000324:Adrenocorticotropic Hormone; D002766:Cholecystokinin; D010418:Pentagastrin; D006854:Hydrocortisone