Secretin and somatostatin as modulators of electrolyte transport in guinea pig gallbladder epithelium.
Effects of secretin and somatostatin on electrolyte transport by guinea pig gallbladder epithelium were investigated in vitro. Tissues were mounted in Ussing-type chambers and continuously short-circuited to measure tissue conductance, short-circuit current (Isc) and transepithelial voltage. Unidirectional fluxes (from mucosa to serosa: Jms; from serosa to mucosa: Jsm) of Na+ and Cl- were determined simultaneously by using tracer techniques and those of HCO3- by pH-stat titration. Serosal addition of secretin caused concentration-dependent increases in tissue conductance, Isc and (lumen-negative) transepithelial voltage. At 1.3 x 10(-8) M, secretin raised net HCO3- secretion by 1.5 mumol/cm2/hr, due to inhibition of Jms (from approximately 1.2 to approximately 0.7 mumol/cm2/hr) and stimulation of Jsm (from approximately 3.7 to approximately 4.7 mumol/cm2/hr). The associated increase in Isc by approximately 3.8 mumol/cm2/hr (up from approximately 0.5 mumol/cm2/hr) was not different from net HCO3-secretion (approximately 4 mumol/cm2/hr). Neither Na+ nor Cl- net fluxes accounted for secretin-induced Isc, both being absorbed at equal rates (Na+: approximately 2.7, down from approximately 4.6 mumol/cm2/hr; Cl-: approximately 2.5, down from approximately 6.4 mumol/cm2/hr). Secretin caused a 10-fold rise of luminal efflux of cyclic AMP that was mitigated by somatostatin, added at 6 x 10(-7) M to the serosal bath. Somatostatin inhibited secretin- and prostaglandin E1-induced Isc, but was ineffective in tissues stimulated with 8-Br-cyclic AMP. It partly reverted the effects of secretin on JmsHCO3 and JsmHCO3, but had no effects in untreated tissues. Our data indicate that secretin converts HCO3-secretion from an electroneutral into an electrogenic process and blocks part of NaCl absorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Sprakties
G
G
Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Rheinisch-Westfälische Hochschule Aachen, Federal Republic of Germany.
Macherey
H J
HJ
Petersen
K U
KU
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D012633:Secretin / Q000494:pharmacology*; D013004:Somatostatin / Q000494:pharmacology*
D004573:Electrolytes; D012633:Secretin; D013004:Somatostatin; D000242:Cyclic AMP