Peptides of human immunodeficiency virus (HIV) evoke rat colonic electrolyte secretion inhibitable by the somatostatin analog octreotide.
An integral transmembrane glycoprotein of the Human Immunodeficiency Virus (HIV) is gp 41. Five peptides (P1, P2, P3, P4, and P5) containing a conserved region of the gp 41 molecule have been synthesized. We tested P3, P4 and P5 for their effects on short-circuit current (Isc) across rat colonic mucosa. All three peptides increased the Isc; P5 was the most potent agonist. Serosal pretreatment of tissues with the chloride transport inhibitor, bumetanide (0.1 mM) or chloride replacement with gluconate, inhibited the response, suggesting that the increase in Isc was due to stimulation of active chloride secretion. The synthetic somatostatin analog octreotide (0.1 mM) also inhibited (P less than .05) the response to P5 (1 microM). The data provide a possible rationale for one aspect of the efficacy of octreotide in treating secretory diarrhea in patients with Acquired Immunodeficiency Syndrome (AIDS).
Fassler
J E
JE
Ohio State University, College of Medicine, Columbus 43210.
O'Dorisio
T M
TM
Goddard
C G
CG
Gaginella
T S
TS
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D003106:Colon / Q000502:physiology; D004553:Electric Conductivity; D015700:HIV Envelope Protein gp41 / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D010455:Peptides; D002034:Bumetanide; D015282:Octreotide