title: Alpha 1-adrenergic control of chloride transport in the rat S1 proximal tubule.
abstract: To identify in vivo the specific alpha-adrenergic receptor mediating direct neural control of chloride transport in the rat S1 proximal convoluted tubule (PCT), the major effector site of neural regulation, microperfusion was employed in conjunction with the alpha 1- and alpha 2-adrenergic receptor antagonists, prazosin and rauwolscine. Using a glomerular ultrafiltrate-like perfusate, prazosin markedly inhibited chloride transport by -42% (302 +/- 10 to 176 +/- 5 peq.mm-1.min-1, P < 0.0001). Using a sodium chloride perfusate, which measures the active component of chloride absorption (J(Cl)act) (control, 153 peq.mm-1.min-1) plus a constant passive (479 peq.mm-1.min-1) component, both prazosin and acute renal denervation reduced J(Cl)act by -38% and -44% (-58 and -67 peq.mm-1.min-1, each P < 0.05). In contrast, rauwolscine caused no significant change in J(Cl)act using either perfusate. Prazosin regulates chloride transport via protein kinase C (PKC), since preactivation of PKC by phorbol abolished inhibitory impact of prazosin. Inhibition of J(Cl)act by prazosin (-58 peq.mm-1.min-1) was fully additive to either the stimulation or inhibition (losartan) of angiotensin II (55 or -49 peq.mm-1.min-1), which uses the adenosine 3',5'-cyclic monophosphate (cAMP) second messenger system [observed changes, not significantly different from 0 and -99 peq.mm-1.min-1; expected changes, not significantly different from 0 and -107 peq.mm-1.min-1]. In conclusion, neural control of S1 PCT chloride absorption in vivo is mediated by alpha 1-adrenergic receptors, which can selectively regulate J(Cl)act by altering PKC activity, independently of the cAMP second messenger system.
authors.affiliation: Department of Medicine, University of California, San Francisco 94121, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Wong
authors.forename: C A
authors.initials: CA
authors.lastname: Berry
authors.forename: M G
authors.initials: MG
authors.lastname: Cogan
mesh_terms: D000042:Absorption; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D007668:Kidney / Q000294:innervation; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D002712:Chlorides; D011942:Receptors, Adrenergic, alpha; D000242:Cyclic AMP; D011493:Protein Kinase C