Functional characterization of the alpha adrenergic receptor modulating the hydroosmotic effect of vasopressin on the rabbit cortical collecting tubule

R. K. Krothapalli, W. N. Suki

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

To characterize the type of alpha adrenergic receptor, the effects of specific alpha adrenergic agonists and antagonists on antidiuretic hormone ([Arg8]vasopressin [AVP])-induced water absorption were evaluated in cortical collecting tubules isolated from the rabbit kidney and perfused in vitro. In the presence of AVP (100 μU/ml), net fluid volume absorption (J(v), nanoliters per minute per millimeter) was 1.39±0.09 and osmotic water permeability coefficient (P(f) x 10-4 centimeters per second) was 150.2±15.0. The addition of 10-6 M phenylephrine (PE), an alpha adrenergic agonist, resulted in a significant decrease in J(v) and P(f) to 0.72±0.11 (P < 0.005) and 69.9±10.9 (P < 0.005). The addition of 10-4 M prazosin (PZ), an alpha1 adrenergic antagonist, did not cause any significant change in J(v) and P(f), which were 0.71±0.09 (P = NS vs. AVP + PE) and 67.8±9.5 (P = NS vs. AVP + PE), respectively. In a separate group of tubules, in the presence of AVP (100 μU/ml) and PE (10-6 M), J(v) and P(f) were 0.78±0.17 and 76.1±18.0, respectively. The addition of 10-6 M yohimbine (Y), an alpha2 adrenergic antagonist, resulted in a significant increase in J(v) to 1.46±0.14 (P < 0.01) and P(f) to 157.5±22.3 (P < 0.005). Y (10-4 M) or PZ (10-4 M) alone did not significantly affect J(v) and P(f) in the presence of AVP (100 μU/ml). The effect of the natural endogenous catecholamine norepinephrine (NE) on J(v) and P(f) in the presence of AVP and propranolol (PR) was next examined. J(v) and P(f) were 1.53±0.07 and 176.3±5.2, respectively, in the presence of AVP (100 μU/ml) and PR (10-4 M). The addition of NE (10-8 M) resulted in a significant decrease in J(v) to 1.19±0.11 (P < 0.05) and P(f) to 127.0±11.3 (P < 0.02). Increasing the concentration of NE to 10-6 M resulted in a further decrease in J(v) and P(f) to 0.70±0.10 (P < 0.01 vs. NE 10-8 M) and 68.5±10.6 (P < 0.01 vs. NE 10-8 M), respectively. The inhibitory effect of NE on AVP-induced water absorption was blocked by Y, but not by PZ. The effect of the alpha2 adrenergic agonist clonidine (CD) on J(v) and P(f) was also examined. In the presence of AVP (10 μU/ml), J(v) and P(f) were 1.65±0.04 and 175.1±13.1, respectively. The addition of CD (10-6 M) resulted in a significant decrease in J(v) to 1.08±0.12 (P < 0.01) and P(f) to 108.1±15.4 (P < 0.01). Increasing the concentration of CD to 10-4 M resulted in a further significant decrease in J(v) and P(f) to 0.57±0.13 (P < 0.02 vs. CD 10-6 M) and 54.7±13.8 (P < 0.01 vs. CD 10-6 M), respectively. Similar results were obtained in the presence of AVP (100 μU/ml). The inhibitory effect of CD on AVP-induced water absorption was blocked by Y. CD did not significantly affect J(v) and P(f) in the presence of 8-bromo adenosine 3',5'-cyclic monophosphate. These studies indicate that alpha adrenergic agonists directly inhibit AVP-mediated water absorption at the level of the renal tubule, an effect that can be blocked by specific alpha2 adrenergic antagonists, but not by specific alpha1 adrenergic antagonists. Alpha2 adrenergic stimulation directly inhibits AVP-mediated water absorption at the level of the tubule, an effect that can be blocked by a specific alpha2 adrenergic antagonist. This effect appears to be exerted at the level of activation of adenylate cyclase, since it is absent in the presence of cyclic AMP.

Original languageEnglish (US)
Pages (from-to)740-749
Number of pages10
JournalJournal of Clinical Investigation
Volume73
Issue number3
DOIs
StatePublished - 1984

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Functional characterization of the alpha adrenergic receptor modulating the hydroosmotic effect of vasopressin on the rabbit cortical collecting tubule'. Together they form a unique fingerprint.

Cite this