Beta-adrenergic, angiotensin II, and bradykinin receptors enhance neurotransmission in human kidney.
The aim of this study was to investigate angiotensin II (Ang II) receptor-, bradykinin receptor-, and beta-adrenergic receptor-mediated modulation of norepinephrine release from human renal sympathetic nerves and to characterize the respective receptor subtypes involved. Human cortical kidney slices were incubated with [3H]norepinephrine, placed in superfusion chambers between two platinum electrodes, and superfused with Krebs-Henseleit solution. The sympathetic nerves were stimulated electrically at 2.5 Hz for 1 minute, and the stimulation-induced outflow of radioactivity was taken as an index of endogenous norepinephrine release. Ang II and its precursor Ang I (both 0.01 to 1 mumol/L) enhanced stimulation-induced outflow of radioactivity in a concentration-dependent manner, with EC50 values of 0.03 and 0.05 mumol/L, respectively. The enhancement by Ang I but not that by Ang II was inhibited by the angiotensin-converting enzyme inhibitor captopril (3 mumol/L). The concentration-response curves of Ang I and Ang II were shifted to the right by EXP 3174 (0.01 mumol), the in vitro active form of the Ang II type 1 receptor antagonist losartan, with affinity estimates of 8.72 and 9.30, respectively. A higher concentration of EXP 3174 (0.1 mumol/L) abolished the facilitatory effects of Ang I and Ang II. The Ang II type 2 receptor antagonist PD 123319 (10 mumol/L) did not alter the facilitation by Ang II. In the absence of other drugs, bradykinin (0.01 to 1 mumol/L) failed to modulate stimulation-induced outflow of radioactivity but in the presence of captopril (3 mumol/L) enhanced it in a concentration-dependent manner, with an EC50 of 0.1 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)
Rump
L C
LC
Innere Medizin IV und Urologie, Universitätsklinik Freiburg, Germany.
Bohmann
C
C
Schaible
U
U
Schultze-Seemann
W
W
Schollmeyer
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000294:innervation*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000502:physiology*; D018002:Receptors, Bradykinin / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011943:Receptors, Adrenergic, beta; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D000804:Angiotensin II; D007545:Isoproterenol; D001920:Bradykinin; D009638:Norepinephrine