Excitatory effect of substance P in parasympathetic ganglia of cat urinary bladder.
Intra-arterial administration of substance P (0.1-50 micrograms/kg) to the urinary bladder of the cat produced slow-onset and sustained bladder contractions, asynchronous firing of bladder postganglionic nerves, and facilitation of nicotinic transmission in bladder ganglia. Intracellular recording from bladder ganglia in vitro revealed that substance P depolarized ganglion cells and initiated burst of action potentials (maximal frequency 6-7 Hz). The ganglionic excitatory effect of substance P in situ was blocked by gamma-aminobutyric acid (2-20 micrograms/kg) and the substance P antagonist [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.5-20 micrograms/kg) but was not altered by atropine (10-100 micrograms/kg), hexamethonium (0.5-2 mg/kg), norepinephrine (2-20 micrograms/kg), or leucine enkephalin (0.5-20 micrograms/kg). The bladder contractions elicited by substance P were not blocked by atropine, hexamethonium, or [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.1-10 micrograms/kg) but were blocked by another substance P antagonist, [D-Pro2,D-Phe7,D-Trp9]substance P. These data indicate that substance P has a direct postsynaptic excitatory effect on neurons in the vesical parasympathetic ganglia and on bladder smooth muscle cells. The differential effects of substance P antagonists on the excitatory responses at these two sites indicate the responses were mediated by different types of tachykinin receptors.
Kawatani
M
M
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Whitney
T
T
Booth
A M
AM
de Groat
W C
WC
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D004743:Enkephalin, Leucine / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005726:Ganglia, Parasympathetic / Q000187:drug effects / Q000502:physiology*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D006584:Hexamethonium Compounds; D013373:Substance P; D018738:Hexamethonium; D005680:gamma-Aminobutyric Acid; D004743:Enkephalin, Leucine; D001285:Atropine; D009638:Norepinephrine