Beta-1 adrenergic inhibition of kallikrein release from rat kidney cortical slices.
Renal storage; release, and biosynthesis of kallikrein were studied using rat cortical slices. This model permitted the study of the direct effect of norepinephrine on the renal kallikrein system in the absence of changes in perfusion pressure. Kallikrein was measured by its kininogenase activity and its direct immunoreactive concentration. Under basal conditions, rat kidney cortical slices synthesize and release glandular kallikrein in vitro at a linear rate for up to 40 min. Kidney slices obtained from rats fed with a low-sodium diet (LS) released more kallikrein into the incubation medium than slices from rats under a normal-sodium diet (NS). Cycloheximide and incubation at 4 degrees C inhibited the release and the biosynthesis of kallikrein independently of the sodium diet. Addition of norepinephrine (NE, 10(-8)-10(-5) M) induced a similar dose-dependent inhibition of kallikrein secretion, which reached -27 +/- 8% in NS rats and -29 +/- 9% in LS rats with 10(-7) M NE. This inhibition of the secretion was associated with an increase in tissue kallikrein concentration in kidney slices from rats on both sodium diets. However, a significant inhibition of the calculated net de novo synthesis was only observed in LS rats. In both groups of animals the ratio of active to total kallikrein was unchanged. The inhibitory effect of kallikrein secretion by NE was never modified in the presence of the alpha-antagonist phentolamine (10(-6) M). In contrast the beta-antagonist propranolol (10(-6) M) prevented the inhibitory effect of 10(-7) M NE.(ABSTRACT TRUNCATED AT 250 WORDS)
Girolami
J P
JP
Institut National de la Santé et de la Recherche Médicale U 133, Toulouse, France.
Bascands
J L
JL
Valet
P
P
Pecher
C
C
Cabos
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D007610:Kallikreins; D009638:Norepinephrine