V1 receptors in luminal action of vasopressin on distal K+ secretion

Abstract

Luminal perfusion with collected proximal fluid increases distal K+ secretion compared with artificial solutions. Arginine vasopressin (AVP), present in luminal fluid, might be responsible for this observation. K+ secretion rate ( J K) was measured by K+-sensitive microelectrodes during paired luminal stationary microperfusion with control and AVP-containing 0.5 mM K+ solutions. J K was 1.34 ± 0.35 ( n = 24 tubules) nmol ⋅ cm− 2 ⋅ s− 1during perfusion with 10− 9 M AVP, against 0.90 ± 0.12 nmol ⋅ cm−2 ⋅ s−1( n = 21) in control ( P < 0.02). With 10− 9 M AVP+10− 6 M β-mercapto-β-β-cyclopenta-methylenepropionyl1, O-Me-Tyr2-Arg8 vasopressin (MCMV), a specific peptide V1-receptor antagonist, J K was 0.36 ± 0.067 against 0.77 ± 0.10 (control; n = 9) nmol ⋅ cm− 2 ⋅ s− 1( P < 0.01). With 10− 6 M MCMV alone, J K was 0.37 ± 0.04 against a control of 0.62 ± 0.06 ( n = 19) nmol ⋅ cm− 2 ⋅ s− 1( P < 0.01). A peptide V2 antagonist had no such effect. In Brattleboro rats, which do not produce endogenous AVP, MCMV had no effect when given alone, although AVP still stimulated J K. In conclusion, luminal AVP stimulates distal J K significantly. The V1 antagonist MCMV inhibits the effect of AVP but also reduces J Kwhen given alone. This suggests that AVP acts luminally via V1 receptors but also that there appears to be a background effect of endogenous AVP blocked by the antagonist.