Ca++ utilization in the constriction of rat aorta to full and partial alpha-1 adrenoceptor agonists.
l-Norepinephrine and l-phenylephrine were full agonists and cirazoline, SKF d-89748, Sgd 101/75 and SKF l-89748 were partial agonists in contracting rat isolated aortic rings. Clonidine, l-amidephrine and St 587 were found ineffective. Nifedipine (10(-8)-10(-6) M) abolished the contractions to Sgd 101/75 and to high K+ with similar potency but only partially inhibited the contractions to the other alpha adrenoceptor agonists. Norepinephrine, phenylephrine, cirazoline and Sgd 101/75 were full agonists in stimulating 45Ca++ influx, which amounted to 50% of the maximal influx produced by high K+. SKF d- and l-89748 behaved as partial agonists, whereas St 587, amidephrine and clonidine were virtually inactive. Nifedipine was equally effective in blocking the influx of 45Ca++ produced by K+ and the alpha adrenoceptor agonists. Norepinephrine stimulated 45Ca++ efflux to an extent similar to that for high K+. In the following order of decreasing efficacy, phenylephrine, cirazoline and SKF d- and l-89748 caused significant stimulation of 45Ca++ efflux. Sgd 101/75, amidephrine, clonidine and St 587 were without effect. However, Sgd 101/75 (10(-5) M) antagonized the 45Ca++ efflux of norepinephrine. Nifedipine (3 X 10(-7) M) completely suppressed the K+-induced 45Ca++ efflux but only partly affected the 45Ca++ efflux caused by the alpha adrenoceptor stimulants. A highly significant (r = 0.975) linear relationship was found between the nifedipine-resistant contractile response and the 45Ca++ efflux obtained in the presence of nifedipine. The data suggest that the stimulation of alpha-1 adrenoceptors in rat aorta can activate two distinct processes of Ca++ utilization for contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Chiu
A T
AT
McCall
D E
DE
Thoolen
M J
MJ
Timmermans
P B
PB
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D004983:Ethanolamines; D007093:Imidazoles; D013764:Tetrahydronaphthalenes; C030655:St 587; D010656:Phenylephrine; C016980:amidephrine; C039140:SK&F 89748; D003000:Clonidine; C034204:indanidine; C014282:cirazoline; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine