Cholera toxin and Gs protein modulation of synaptic transmission in guinea pig mesenteric artery.
Cholera toxin (CTX) was used to test whether the presynaptic beta-adrenoceptors of guinea-pig mesenteric artery are coupled via stimulatory GTP-binding proteins. The vascular smooth muscle cells were electrically quiescent unless stimulated and had a mean resting potential of -68.7 +/- 2.8 mV (n = 16) and input resistance of 12.1 +/- 0.5 M omega (n = 4). Perivascular nerve stimulation with brief square pulses evoked excitatory junction potentials (EJPs) in the muscle cells. Isoproterenol (0.1 microM) enhanced the EJP amplitude without modifying the passive membrane properties of the muscle cells. The beta-blocker, propranolol (0.5 microM), prevented the effects of isoproterenol on EJP amplitude. The permeant analogue of cyclic AMP, 8-bromocAMP, also potentiated EJP amplitude. EJP amplitude was markedly enhanced by treatment of the isolated blood vessels with CTX (10 micrograms/ml for 1 h). The muscle cells became hyperpolarized (-74.6 +/- 2.1 mV, n = 5), and their input resistances were significantly reduced (8.2 +/- 0.5 M omega, n = 4). These effects of CTX persisted after washout. Addition of GM1 ganglioside (5 micrograms/ml) prevented the CTX effects. The CTX enhancement of EJP amplitude was not prevented by application of depolarizing current (ca. 0.5 nA) the muscle cells (to counter the hyperpolarization). These results suggest that CTX increases the neurotransmitter release from the nerve terminals; the hyperpolarization may be due to an increase in K+ conductance. These effects of CTX may be mainly due to elevation of cAMP in the nerve terminal and in the muscle cell.
Nozaki
M
M
Department of Physiology and Biophysics, University of Cincinnati, College of Medicine, OH 45267-0576.
Sperelakis
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D004558:Electric Stimulation; D019204:GTP-Binding Proteins / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009411:Nerve Endings / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013779:Tetrodotoxin; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D007545:Isoproterenol