Differential effect of omega-conotoxin on release of the adrenergic transmitter and the vasoconstrictor response to noradrenaline in the rat isolated kidney.
1. The effects of the Ca2+ channel blockers omega-conotoxin (omega-CgTx), nifedipine and diltiazem, on the increase in tritium overflow and perfusion pressure elicited by renal nerve stimulation (RNS), veratridine (Vt) and potassium chloride (KCl), and on the vasoconstrictor response produced by noradrenaline (NA) were investigated in the isolated kidney of the rat perfused with Tyrode solution and prelabelled with [3H]-noradrenaline ([3H]-NA). 2. RNS (1-4 Hz), Vt (15-90 nmol) and KCl (150-500 mumol) produced renal vasoconstriction and enhanced the tritium overflow in a frequency- and concentration-dependent manner, respectively. 3. Administration of omega-CgTx (50 nM) inhibited RNS-, Vt- and KCl-induced overflow of tritium; the associated renal vasoconstriction produced by RNS or Vt but not by KCl was inhibited. In contrast, omega-CgTx failed to alter the vasoconstrictor response elicited by exogenous NA. 4. Infusion of nifedipine (10 microM) enhanced the tritium overflow elicited by RNS and KCl but not by Vt; a low dose of nifedipine (1.4 microM) enhanced the tritium overflow elicited by all these stimuli. Low doses of diltiazem (6 microM) failed to alter the tritium overflow produced by these stimuli. However, higher doses of diltiazem (60 microM) reduced the tritium overflow elicited by RNS or Vt but enhanced that caused by KCl. The renal vasoconstriction produced by RNS, Vt and KCl as well as by exogenous NA was inhibited by low and high doses of nifedipine and diltiazem. 5. These data suggest that (a) RNS, Vt and KCl enhance the release of adrenergic transmitter by promoting the influx of Ca2+ into the nerve terminal through specific Ca2+ channels, probably N-type Ca2+ channels that are distinct from those located in the vascular smooth muscle and (b) co-CgTx could be a useful tool to differentiate between Ca2+ channels at the adrenergic nerve terminal and vascular smooth muscle.
el-Din
M M
MM
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Malik
K U
KU
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000032:analysis; D007668:Kidney / Q000098:blood supply* / Q000294:innervation; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*; D014701:Veratridine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D007473:Ion Channels; D008978:Mollusk Venoms; D011189:Potassium Chloride; D014701:Veratridine; D020866:omega-Conotoxin GVIA; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine