Abstract
We compared the effects of dopamine and norepinephrine on vasopressin (AVP)-stimulated increases in osmotic water permeability (Pf) and cAMP accumulation in the rat inner medullary collecting duct (IMCD). Both dopamine and norepinephrine inhibited AVP-induced Pf and cAMP accumulation in a concentration-dependent manner; however, norepinephrine was approximately 100-fold more potent than dopamine. The effects of dopamine on Pf were antagonized by the selective α2-adrenoceptor antagonist, rauwolscine (10 nM–1 μM). Clozapine (10 μM), a dopamine D4 receptor antagonist with significant activity at adrenergic receptors, partially attenuated both dopamine and norepinephrine-induced decreases in AVP-stimulated Pf. Dopamine-induced inhibition of AVP-dependent cAMP levels was antagonized by the α2-adrenoceptor antagonists, rauwolscine, idazoxan, and yohimbine, but not by the dopamine receptor antagonists, spiperone, SCH-23390, or raclopride. Clozapine (1–10 μM) inhibited the effects of both dopamine and norepinephrine on AVP-stimulated cAMP levels. We conclude that the inhibitory effects of dopamine on AVP-induced Pf and cAMP accumulation in the rat IMCD are mediated via α2-adrenoceptors.
Footnotes
- Abbreviations:
- IMCD
- inner medullary collecting duct
- AVP
- arginine vasopressin
- Pf
- osmotic water permeability
- CPT-cAMP
- 8-p-chlorophenylthio-cAMP
- Received April 20, 2001.
- Accepted May 22, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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