Vasopressin neuromodulation in the hippocampus.
This study explored an effector mechanism associated with the arginine vasopressin (AVP) recognition site in the hippocampus, namely, potentiation of norepinephrine (NE)-induced cAMP accumulation in the surviving hippocampal slice. The biochemical mechanisms that underlie the AVP potentiation were investigated as follows: First, the actions of AVP upon NE-induced accumulation of cAMP in hippocampal slices from rat brain were specific to AVP and not shared by other closely related peptides, namely, oxytocin and AVP4-9. Second, the AVP-induced neuromodulation involved beta-adrenergic receptors, with AVP having no effect on cAMP levels in the absence of NE. Third, the potentiation by AVP was biphasic, with lower AVP concentrations potentiating NE-induced cAMP accumulation, while higher concentrations did not potentiate. Fourth, an antagonist of V1-type AVP receptors blocked AVP potentiation. Fifth, AVP potentiation was dependent upon extracellular calcium concentrations. Sixth, AVP potentiation was blocked by 50 microM trifluoperazine, which is consistent with a calcium-calmodulin involvement but which might also implicate protein kinase C. These alternatives and the nature of the calcium involvement are discussed. AVP actions thus appear to involve interactions between several second-messenger systems and suggest a biochemical mechanism by which AVP exerts its centrally mediated behavioral effects.
Brinton
R E
RE
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.
McEwen
B S
BS
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000502:physiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D014667:Vasopressins / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D014667:Vasopressins; D001127:Arginine Vasopressin; D005576:Colforsin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D000242:Cyclic AMP; D002118:Calcium; D009638:Norepinephrine