Hydrocortisone treatment increases the sensitivity and responsiveness to cholecystokinin in rat pancreas.
The effects of hydrocortisone treatment on the secretory abilities of pancreatic acini to various secretagogues were studied. Rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, or 5.0 mg/kg body wt once daily for 7 days. Hydrocortisone led to a small dose-dependent increase in pancreatic wet weight per 100 g body wt, which was associated with an increase in both total protein and DNA contents. In acini prepared from hydrocortisone-treated rats, both the responsiveness and the sensitivity to cholecystokinin octapeptide (CCK-8) was increased. The concentration dependence of cellular Ca2+ mobilization in response to CCK-8 was also shifted to lower concentrations in acini from hydrocortisone-treated rats compared with control rat acini. In vivo administration of hydrocortisone caused a significant increase in the affinity of 125I-CCK-8 binding to high-affinity receptors. The secretory responsiveness to carbamylcholine and bombesin, but not to secretin, was also increased but without any change in the sensitivity. Moreover, the hydrocortisone treatment increased the secretory responsiveness of acini to the Ca2+ ionophore A23187 and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate but did not to an adenosine 3',5'-cyclic monophosphate analogue, 8-bromoadenosine 3',5'-cyclic monophosphate. The present observations suggest that in vivo glucocorticoid administration affects both the CCK receptors and a postreceptor loci.
Otsuki
M
M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Okabayashi
Y
Y
Nakamura
T
T
Fujii
M
M
Tani
S
S
Ohki
A
A
Baba
S
S
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002469:Cell Separation; D002766:Cholecystokinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000502:physiology; D012633:Secretin / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011949:Receptors, Cholecystokinin; D012633:Secretin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D002217:Carbachol; D002766:Cholecystokinin; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin; D002118:Calcium; D006854:Hydrocortisone