The role of CGRP and afferent nerves in the modulation of pancreatic enzyme secretion in the rat.
CONCLUSIONS
Stimulation of pancreatic sensory nerves by capsaicin produced secretory effects probably caused, at least in part, by the release of CGRP.


BACKGROUND
In the pancreas calcitonin gene-related peptide (CGRP) has been localized in the sensory nerves, but its physiological role is unknown. This study was undertaken to compare the changes of pancreatic enzyme secretion produced by CGRP and by stimulation or destruction of sensory nerves.


METHODS
To stimulate sensory nerves, low doses of capsaicin (0.25-0.5 mg/kg) were given intraduodenally to the conscious rats with chronic pancreatic fistula. To inactivate sensory nerves high doses of capsaicin (100 mg/kg) were given subcutaneously 10 d before tests. For the in vitro experiments pancreatic slices and isolated pancreatic acini were prepared from intact and capsaicin-denervated rats.


RESULTS
In conscious rats, CGRP given subcutaneously (5-10 micrograms/kg) and low doses of capsaicin given intraduodenally reduced basal pancreatic secretion. In isolated pancreatic acini, CGRP (10(-10)-10(-6) M), but not capsaicin, increased basal or secretagog-stimulated amylase release. In pancreatic slices (containing nerve fibers) capsaicin (10(-10)-10(-6) M) increased enzyme secretion, and this secretion was abolished by previous inactivation of sensory nerves by this neurotoxin. Capsaicin deactivation did not affect the secretory response of pancreatic acini to CGRP, cerulein, or urecholine. Sensory denervation by capsaicin did not change basal protein secretion, but reduced that produced by feeding or diversion of pancreatic juice to the exterior during first 2 h of the tests.
Jaworek
J
J
Institute of Physiology, Colleguim Medicum Jagiellonian University, Kraków, Poland.
Konturek
S J
SJ
Szlachcic
A
A
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001626:Bethanechol Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin / Q000008:administration & dosage; D002108:Ceruletide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010179:Pancreas / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D010185:Pancreatic Fistula; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001626:Bethanechol Compounds; D002108:Ceruletide; D000681:Amylases; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin