Cross-desensitization of VIP- and NANC-mediated inhibition of the guinea-pig tracheal pouch.
1. Chloralose/urethane anaesthetized guinea-pigs were used for preparation of the tracheal pouch, which demonstrates the NANC innervation. Isolated vagi cut cranially were positioned on bipolar electrodes for subsequent stimulation. The animals were given atropine and propranolol intraperitoneally before the experimental procedure to assure that responses would be from non-adrenergic, non-cholinergic components. 2. ATP and VIP, two putative neurotransmitters for non-adrenergic, non-cholinergic (NANC) inhibitory innervation caused relaxation responses of the pouch. Both VIP and ATP (10(-9) M) caused auto-desensitization after four repeated administrations into the pouch. 3. If NANC nerve stimulation causes relaxation of tracheal smooth muscle by release of one of these agents onto a specific receptor, repeated exposure to that agent by nerve stimulation or exogenous application could cause diminished responsiveness from cross-desensitization, yet maintained responsiveness to an agent acting at other receptors. 4. Relaxation responses to vagal stimulation were determined before and after the pouch was incubated for a 10-min period with either ATP or VIP (10(-6) M). ATP incubation did not produce significant (P less than 0.05) change in the degree of relaxation in response to nerve stimulation. In contrast, VIP incubation did cause diminished relaxation of the pouch in response to subsequent nerve stimulation. 5. The ability of the agents at 10(-9) M and 10(-6) M to cause relaxation of the pouch was next examined before and after repeated NANC nerve stimulation. Relaxation of the pouch to ATP was not significantly affected by intervening repeated nerve stimulations. However, relaxation in response to VIP was significantly inhibited by repeated nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Venugopalan
C S
CS
Department of Veterinary Physiology, Pharmacology and Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803.
O'Malley
N A
NA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D014132:Trachea / Q000294:innervation / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*
D014660:Vasoactive Intestinal Peptide; D000255:Adenosine Triphosphate