Abnormal agonist-stimulated cardiac parasympathetic acetylcholine release in streptozocin-induced diabetes.
We examined the effect of three distinct depolarizing conditions on [3H]ACh release from cardiac postganglionic parasympathetic neurons in age-matched controls and insulin-treated STZ-induced diabetic rats to determine whether alterations in neurotransmitter release were present in the diabetic group. The effect of TTX, which exerts a use- and voltage-dependent block of sodium channels, was examined on the release of ACh stimulated by SRIF14 (preferentially acts at the cell body). We also studied the effect of STZ-induced diabetes on [3H]ACh release by the relatively site-specific depolarizing agent VT (preferentially acts at the axon) and high potassium (non-site-specific). Basal, SRIF14-(10(-7) M), VT-(10(-4) M), and K+ (100 mM)-stimulated [3H]ACh release was similar in control and STZ-induced diabetic animals. However, in STZ-induced diabetic but not control rats, SRIF14-induced [3H]ACh release was resistant to TTX (2 x 10(-7) M). In addition, the response to submaximal K+ (25 mM) stimulation was greater in STZ-induced diabetic compared with control animals. Treatment with insulin corrected these abnormalities. These data indicate that in the acute STZ-induced diabetic rat, SRIF14-, VT-, and high K(+)-evoked release of ACH is not impaired, which suggests that the mechanisms associated with ACh storage and release in postganglionic cardiac parasympathetic neurons are not affected in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
Uccioli
L
L
Department of Internal Medicine, Tor Vergata University II, Rome, Italy.
Magnani
P
P
Tilli
P
P
Cotroneo
P
P
Manto
A
A
Greco
A V
AV
Sima
A A
AA
Greene
D A
DA
Menzinger
G
G
Ghirlanda
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006321:Heart / Q000294:innervation*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D013779:Tetrodotoxin; D013004:Somatostatin; D014701:Veratridine; D000109:Acetylcholine