Evidence for beta adrenoceptors in proximal tubules: Isoproterenol-sensitive adenylate cyclase in pars recta of canine nephron

Abstract

Observations in vivo suggest that catecholamines modulate reabsorptive functions of proximal tubules by acting on β-adrenoceptors. However, β-catecholamine binding sites or β-adrenoceptor-sensitive adenylate cyclase (AdC) has not been found in segments of proximal tubules of rat, rabbit, or mouse kidney. In the present study, we investigated the responsiveness of AdC to catecholamines, [8-Arg]vasopressin (AVP), and to parathyroid hormone (PTH) in proximal convoluted tubules (PCT), proximal straight tubules (PST), and in late distal convoluted tubules (LDCT) microdissected from canine kidney. Isoproterenol (ISO) caused a marked and dose-dependent stimulation of AdC in PST (maximum: Δ + 850%; half maximum stimulation at 10-7 M ISO), but ISO had no effect on AdC in PCT. The AdC in both PCT and PST was markedly stimulated by PTH; AVP stimulated the AdC in LDCT but not in PST or in PCT. The stimulatory effect of 10-5 M ISO in PST (Δ + 725%) was significantly greater than in LDCT (Δ + 307%); norepinephrine and epinephrine had stimulatory effects in PST similar to ISO. The stimulation of AdC in PST by ISO was blocked by propranolol and by β2-blocker ICI-118551. On the other hand, α-blocker phentolamine and β1-blocker metoprolol did not abolish the stimulation of AdC in PST by ISO. The accumulation of cAMP in intact PCT and PST incubated in vitro was stimulated by PTH both in PST and in PCT, but ISO elevated cAMP (Δ + 683%) only in PST. Our results show that proximal tubules of canine nephron, PST but not PCT, contain β-adrenoceptors of β2 subtype coupled to AdC. These observations provide direct evidence that the effects of catecholamines, either released from renal nerve endings or arriving from blood supply, can act directly on β2-adrenoceptors located in proximal tubules, and also suggest that at least some of the catecholamine effects in proximal tubules are mediated via cAMP generation.