Putrescine uptake in rat pancreatic acini: effect of secretagogues and growth factors.
Polyamines [putrescine (Put), spermidine, and spermine] are normal cellular constituents that can modulate cellular proliferation and differentiation in a number of tissue and cell types. Transport is one of the mechanisms that control intracellular polyamine content. The present investigation explores the influence of cholecystokinin (CCK), other secretagogues [carbachol, bombesin, vasoactive intestinal polypeptide (VIP)], insulin, insulin-like growth factor 1 (IGF-1), and epidermal growth factor (EGF) on Put uptake in rat pancreatic acini. Insulin, IGF-1, and EGF stimulated Put uptake by 30-40%. Insulin did not enhance intracellular metabolism of Put. In contrast, CCK and the other secretagogues inhibited this transport system by 40-50% of control (VIP by 23% only). Further investigations of the inhibitory effect of CCK revealed that the maximal uptake rate of Put (Vmax) shifted from 346 pmol [14C]Put/mg DNA-min (control) to 265 pmol [14C]Put/mg DNA-min (100 pM CCK), whereas the Km was only moderately influenced. Augmented Put efflux as well as increased production of endogenous Put (possibly induced by CCK) did not contribute to this change in transport kinetics. In addition, the inhibition of Put uptake induced by CCK was specific and dose dependent up to 100 pM. CCK at 1,000 pM exerted only minor inhibition (20% of control). Incubation with the Ca-ionophore A 23187 did not influence Put accumulation, whereas treatment with the phorbol ester phorbol 12-myristate-13-acetate led to enhanced Put uptake (30-40%). Pretreatment of the acini with 1 mM ouabain led to a reduction of Put uptake by 43%.(ABSTRACT TRUNCATED AT 250 WORDS)
Stüber
E
E
Division of Gastroenterology and Endocrinology, Georg August University, Göttingen, Germany.
Alves
F
F
Höcker
M
M
Fölsch
U R
UR
D000818:Animals; D001839:Bombesin / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D011700:Putrescine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology
D006133:Growth Substances; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol; D002766:Cholecystokinin; D012844:Sincalide; D001839:Bombesin; D011700:Putrescine