Angiotensin II receptors in Xenopus oocytes.
Electrical recordings were used to study the sensitivity of native Xenopus oocytes to the octapeptide angiotensin II (AII). AII elicited oscillatory currents associated with an increase in membrane conductance to Cl-. Responsiveness to AII varied greatly between oocytes taken from different frogs, and to a lesser extent between oocytes from the same ovary. Oocytes from frogs showing high sensitivity had response thresholds between 0.5-1.0 nM AII, and at a holding potential of -60 mV, responded to 1 microM AII with currents greater than 3 microA. In contrast, oocytes from some frogs gave no response, even to 10 microM AII. A total of 618 oocytes from 79 frogs were tested for sensitivity to AII, and oocytes from 85% of frogs gave detectable electrical responses. Oscillatory Cl- currents elicited by AII were largely independent of extracellular Ca2+, were abolished by chelation of intracellular Ca2+ using EGTA and were mimicked by intraoocyte injection of inositol 1,4,5-trisphosphate (IP3). In addition to oscillatory Cl- currents, AII also evoked an influx of extracellular Ca2+, giving rise to a transient inward Cl- current on membrane hyperpolarizing steps. These experiments all suggested that AII responses were elicited through activation of an intracellular messenger pathway triggered by hydrolysis of inositolphospholipids, mobilization of intracellular Ca2+ by inositol polyphosphates, and activation of Ca(2+)-gated Cl- channels. The effect of manual or enzymic defolliculation on AII responses was studied in nine separate experiments recording from 70 defolliculated oocytes. Efficacy of defolliculation procedures was assayed using scanning electron microscopy, which confirmed removal of 90 to greater than 98% of follicular cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Woodward
R M
RM
Department of Psychobiology, University of California, Irvine 92717.
Miledi
R
R
D000200:Action Potentials / Q000187:drug effects; D000595:Amino Acid Sequence; D000803:Angiotensin I / Q000737:chemistry; D000804:Angiotensin II / Q000737:chemistry / Q000494:pharmacology; D000805:Angiotensin III / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005260:Female; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D006080:Ovarian Follicle / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D014982:Xenopus laevis
D002712:Chlorides; D007473:Ion Channels; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D000805:Angiotensin III; D000803:Angiotensin I; D011188:Potassium; D002118:Calcium