Specific inhibition of basal gastric acid secretion by salmon calcitonin in rats does not necessarily involve a central pathway.
It is well established that salmon calcitonin (sCT), given either by central (intracerebroventricular) or peripheral (parenteral) injection is a potent inhibitor of gastric acid secretion. It is generally believed that this effect of sCT is mediated by the central nervous system based on reports that the effective peripheral dose is up to 1000 times greater than the effective dose administered centrally. We have reexamined this hypothesis by carrying out a number of independent experiments in two laboratories on the effect of sCT, given either by intracerebroventricular or by subcutaneous injection, on basal gastric acid secretion in unanaesthetized rats. Statistical evaluation of the data showed the reproducibility of the effective inhibitory dose ranges of sCT despite the inherent variability of the pylorus ligated rat system (Shay test). The effective dose range for sCT given centrally was between three- and ten-fold lower than that for peripherally administered sCT. There is no published evidence that a significant amount of peripherally administered sCT passes through the blood-brain barrier to relevant areas of the brain and this is confirmed in our study by autoradiography of serial sections of brain following intravenous administration of radioiodinated sCT. It therefore appears that the inhibitory effect of sCT, given centrally or peripherally, may not necessarily be mediated by a common pathway in the central nervous system. Our results also show that the inhibitory effect of peripherally administered sCT is lost when rats are treated with cysteamine to deplete somatostatin, thus implicating somatostatin as a peripheral mediator.
Guidobono
F
F
Università degli Studi, Dipartimento di Farmacologia, Milano, Italy.
Netti
C
C
Pecile
A
A
Zanelli
J M
JM
Gaines-Das
R E
RE
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D002490:Central Nervous System / Q000502:physiology; D003543:Cysteamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007457:Iodine Radioisotopes; D008297:Male; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D012474:Salmon; D013004:Somatostatin / Q000502:physiology
D007457:Iodine Radioisotopes; D013004:Somatostatin; D003543:Cysteamine; D002116:Calcitonin