Treatment with pertussis toxin does not prevent central effects of eel calcitonin.
To determine whether or not the CNS inhibitory activity of eel calcitonin (eCT) on adenylyl cyclase is the endocellular mechanism underlying the antinociceptive effect of the peptide, as shown for morphine analgesia, we administered Bordetella pertussis toxin (PTX) by intracerebroventricular (ICV) injection (0.5 microgram/rat) to block the receptor-mediated inhibition of adenylyl cyclase. In PTX-treated rats there was no change in eCT (2.5 micrograms/rat, ICV)-induced antinociceptive activity (hot-plate test) nor in eCT (100 ng/rat, ICV) inhibition of gastric acid secretion (Shay test) whereas morphine (5 micrograms/rat, ICV) analgesia was significantly reduced. In vitro studies showed no reduction of eCT binding in the CNS of rats treated with PTX in vivo. Moreover, PTX treatment did not change the inhibitory effect of eCT on adenylyl cyclase in isolated membranes from rat striatum in contrast with opiates (DAME and morphine) whose effects were lost. As PTX is known to inactivate the guanidine binding inhibitory protein Gi, these data suggest that a G protein, distinct from the Gi protein involved in the coupling of opiate receptors into a functional response, could be responsible for regulating the intracellular pathways resulting in eCT-induced antinociceptive effect and inhibition of gastric acid secretion.
Guidobono
F
F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Bettica
P
P
Villa
I
I
Pagani
F
F
Netti
C
C
Sibilia
V
V
Pecile
A
A
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002116:Calcitonin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009619:Nociceptors / Q000187:drug effects; D010147:Pain Measurement; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D010566:Virulence Factors, Bordetella; D002116:Calcitonin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins