This study determined the fractional extraction of epinephrine and norepinephrine by the in situ dog pancreas. Plasma samples for epinephrine measurements were taken simultaneously from the femoral artery and the superior pancreaticoduodenal vein. Pancreatic extraction of epinephrine was 73 ± 5% when basal arterial epinephrine levels were 380 ± 93 pg/mL, 76 ± 4% when arterial levels were 896 ± 123 pg/mL (epinephrine infused intravenously at 20 ng/kg/min), and 84 ± 1% when arterial levels were 2,956 ± 414 pg/mL (epinephrine infused intravenously at 80 ng/kg/min) suggesting that the process of epinephrine extraction by the pancreas is not saturable over this range. During a similar sampling protocol, norepinephrine was infused intravenously at 4 μg/kg/min; pancreatic extraction of norepinephrine was then 65 ± 7% when arterial norepinephrine levels were 107,000 ± 28,000 pg/mL. In separate experiments, lower rates of norepinephrine (12 to 1,200 ng/min) were infused directly into the pancreatic artery and pancreatic norepinephrine extraction was calculated; it ranged between 66% and 75%. Because the pancreas produces as well as extracts norepinephrine, a third technique was required to determine pancreatic norepinephrine extraction at the lower endogenous levels of norepinephrine; 3H-norepinephrine was infused intravenously and the arteriovenous difference of 3H-norepinephrine was measured. Fractional extraction of 3H-norepinephrine was 74 ± 4% both in the basal state (arterial norepinephrine level = 202 ± 44 pg/mL) and during systemic, glucopenic, stress induced by 2-deoxy-glucose (arterial norepinephrine level = 636 ± 70 pg/mL). These data suggest that also the norepinephrine extraction process by the pancreas is not sarurable. Further, since the pancreatic extraction of norepinephrine is so avid, these data suggest that measurement of the arteriovenous concentration difference of endogenous norepinephrine alone will markedly underestimate local norepinephrine spillover. Correcting these measurements for the extraction would, however, provide an index of the endogenous activity of pancreatic adrenergic nerves. Finally, this study also determined whether pancreatic catecholamine extraction is altered by α-or β-adrenoceptor antagonists; phenoxybenzamine was found to reduce the extraction of both epinephrine (P < .001) and norepinephrine (P < .05) whereas propranolol did not. Thus, one must consider how changes of pancreatic catecholamine extraction might alter the interpretation of experiments using α-adrenoceptor antagonists to study local norepinephrine release or catecholamine effects on pancreatic hormone secretion. In summary, (1) at steady state 60% to 80% of either epinephrine or norepinephrine is extracted in one pass by the dog pancreas, (2) this process of extraction appears nonsaturable, and (3) the pancreatic extraction of catecholamines is impaired by the α-adrenoceptor antagonist phenoxybenzamine, but not by the β-adrenoceptor antagonist propranolol.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism