title: Alpha 1B-receptors and intracellular calcium mediate sympathetic nerve induced constriction of rat irideal blood vessels.
abstract: The present study has investigated the receptors involved in the non-cholinergic nerve mediated constriction of the larger blood vessels (30-50 microns) within the rat iris. This response was blocked by the alpha-adrenoceptor antagonist, benextramine (10(5) M). Furthermore, the response was more sensitive to blockade by the alpha 1 antagonist, prazosin (IC50 9 x 10(-10) M), than to blockade by the alpha 2 antagonist, yohimbine (IC50 2 x 10(-7) M), or the adrenergic antagonist, WB4101 (IC50 2 x 10(-8) M), and was abolished by chloroethylclonidine (10(-5) M). These results suggest the involvement of alpha 1B-adrenoceptors. The nerve mediated constriction was not blocked by the voltage-dependent calcium channel blocking drugs, nifedipine (10(-6) M), verapamil (10(-6) M) or diltiazem (10(-6) M), but was completely abolished by the intracellular calcium mobilizer, caffeine (10(-3) M), supporting the hypothesis that alpha 1B-adrenoceptors are activated following nerve stimulation. Dantrolene (10(-4) M), which interferes with calcium release from the sarcoplasmic reticulum, reduced the nerve mediated constriction by 40% as did thapsigargin (2 x 10(-6) M), which inhibits the calcium ATPase responsible for uptake of calcium into intracellular stores. When influx of calcium was blocked by verapamil (10(-6) M), thapsigargin, but not dantrolene, completely abolished the response. Noradrenaline (10(-5) M) produced a vasoconstriction in the presence or absence of external calcium although the latter response was significantly smaller than the former. Vasoconstriction produced by a submaximal concentration of noradrenaline (10(-6) M), was completely prevented by pretreatment with chloroethylclonidine. The data indicate that noradrenaline released from sympathetic nerves causes a constriction of arterioles in the iris by activating alpha 1B-adrenoceptors and releasing calcium from dantrolene sensitive and insensitive intracellular stores, followed by inflow of calcium through verapamil sensitive calcium channels. Applied noradrenaline also activates chloroethylclonidine sensitive receptors on the arteriolar surface.
authors.affiliation: Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Act.
authors.forename: D J
authors.initials: DJ
authors.lastname: Gould
authors.forename: C E
authors.initials: CE
authors.lastname: Hill
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007498:Iris / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D018340:Receptors, Adrenergic, alpha-1; D002110:Caffeine; C051731:chlorethylclonidine; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine