Interaction between brain L-type calcium channels and alpha2-adrenoceptors in the inhibition of sodium appetite.
Calcium channels mediate the actions of many drugs. The present work investigated whether diltiazem, an L-type calcium channel blocker, alters the inhibition of sodium appetite induced by noradrenaline and the alpha2-adrenoceptor agonist clonidine. Adult male Holtzman rats (N=4-8) with cannula implanted into the third cerebral ventricle were submitted to sodium depletion (furosemide sc+24-h removal of ambiente sodium). Sodium depleted control animals that received 0.9% NaCl as vehicle injected intracerebroventricularly (i.c.v.) ingested 13.0+/-1.5 ml/120 min of 1.8% NaCl. Intracerebroventricular injection of either noradrenaline (80 nmol) or clonidine (20 nmol) inhibited 1.8% NaCl intake from 70 to 90%. Prior i.c.v. injection of diltiazem (6-48 nmol) inhibited from 50 to 100% the effect of noradrenaline and clonidine in a dose-response manner. Diltiazem alone at 100 nmol inhibited, but at 50 nmol had no effect on, sodium appetite. The results suggest: (1) common ionic mechanisms involving calcium channels for the inhibition that noradrenaline and clonidine exert on sodium appetite and (2) a dual role for the benzothiazepine site of L-type calcium channels in the control of sodium appetite.
De Luca
Laurival A
LA
Department of Physiology and Pathology, School of Dentistry, UNESP, 14801-903 Araraquara, São Paulo, Brazil. lucajr@foar.unesp.br
Sugawara
Alexandre M
AM
Pereira
Daniela T B
DT
David
Richard B
RB
Menani
José V
JV
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000172:deficiency; D012982:Sodium, Dietary
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018341:Receptors, Adrenergic, alpha-2; D012982:Sodium, Dietary; D012964:Sodium; D004110:Diltiazem; D003000:Clonidine; D009638:Norepinephrine