Neural blockade in basal and postreceptor-stimulated intestinal transport.
Postreceptor protein stimulation significantly alters the transport state of the ex vivo small intestine. This study investigated the effects of neural blockade on basal and stimulated ionic transport. Rabbit ileal segments (n = 46) were arterially perfused with an oxygenated sanguinous buffered electrolyte solution. The lumen was perfused with an isotonic solution containing [14C]polyethylene glycol as a nonabsorbable marker. Net fluxes of H2O, Na+, and Cl- were calculated. Tetrodotoxin (TTX) was used to block enteric neural transmission. Forskolin (FOR) was used to activate adenylate cyclase, and phorbol 12,13-dibutyrate (PDB) served to activate protein kinase C. Two groups were studied. Group A preparations had no TTX pretreatment, while group B preparations were pretreated with TTX. In the Group A preparations, TTX at 10(-6) M and PDB at 10(-5) M caused significant proabsorptive effects with a delta FH2O of +20 +/- 7 and +15 +/- 2 microliters/min, respectively (P less than 0.05), while FOR stimulated significant secretion with a delta FH2O of -14 +/- 3 microliter/min (P less than 0.05). In the Group B TTX-pretreated preparations, FOR did not cause secretion and PDB maintained an absorptive state. These results indicate that neural blockade with TTX reverses basal secretion in the ex vivo intestine, suggesting that an intact enteric nervous system maintains the secretory status of the intestine. FOR-induced adenylate cyclase-activated secretion does not occur in the presence of TTX, implying that intact neural transmission is required for the FOR effect. PDB-induced protein kinase C-activated absorption occurs despite neural blockade, suggesting that the PDB-induced proabsorptive effect is mediated without neural intermediaries.
Bastidas
J A
JA
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Zinner
M J
MJ
Orandle
M S
MS
Yeo
C J
CJ
D000042:Absorption; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D004573:Electrolytes / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D009407:Nerve Block; D010477:Perfusion; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011312:Pressure; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014867:Water / Q000493:pharmacokinetics
D004573:Electrolytes; D011956:Receptors, Cell Surface; D014867:Water; D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D013779:Tetrodotoxin