Potentiation by Metoclopramide of Responses to Cholinergic Nerve Stimulation in the Isolated Gastric Fundus Preparation of the Rat

Abstract

y b o t h a s an a n t i -e m e t i c and a l s o t o i n c r e a s e t h e r a t e o f g a s t r i c emptying ( P i n d e r g! o t h e r s , 1 9 7 6 ) . The a n t i -e m e t i c e f f e c t o f metoclopramide is p r o b a b l y r e l a t e d t o i t s a c t i o n i n b l o c k i n g dopamine r e c e p t o r s ( p e r i n g e r & o t h e r s , 1975; Day & Blower, 1 9 7 5 ) . However, t h e mechanism o f i t s a c t i o n on t h e g a s t r o i n t e s t i n a l t r a c t i s n o t c l e a r and a number of p o s s i b i l i t i e s have been s u g g e s t e d ( f o r review see P i n d e r & o t h e r s , 1 9 7 6 ) . I n t h e p r e s e n t i n v e s t i g a t i o n t h e a c t i o n o f metoclopramide h a s been examined on t h e smooth muscle o f t h e r a t g a s t r i c fundus p r e p a r a t i o n (Vane, 1957) i n which t h e i n t r i n s i c n e u r a l e l e m e n t s have been a c t i v a t e d by e l e c t r i c a l f i e l d s t i m u l a t i o n . F i e l d s t i m u l a t i o n s were a p p l i e d f o r t r a i n s o f 100 p u l s e s o f supramaximal s t r e n g t h (140 v o l t ) and 2 m.sec p u l s e w i d t h a t f r e q u e n c i e s o v e r t h e r a n g e 0 . 5 t o 20 H e r z . The r e s p o n s e s t o f i e l d s t i m u l a t i o n i n c o n t r o l p r e p a r a t i o n s were f r e q u e n c y -r e l a t e d c o n t r a c t i o n s which were p o t e n t i a t e d by n e o s t i g m i n e (10-100 ng/ml) o r e s e r i n e (10-100 ng/ml) and were a b o l i s h e d by e i t h e r t e t r o d o t o x i n (1 ug/ml) o r a t r o p i n e (20 t o 100 ng/ml). I t was c o n c l u d e d t h a t t h e c o n t r a c t i l e r e s p o n s e s were mediated v i a a c t i v a t i o n o f c h o l i n e r g i c n e r v e e l e m e n t s i n t h e muscle. Metoclopramide ( 1 t o 10 ug/ml) i n c r e a s e d t h e r e s p o n s e s to c h o l i n e r g i c n e r v e s t i m u l a t i o n a t a l l f r e q u e n c i e s of s t i m u l a t i o n a l t h o u g h t h e e f f e c t w a s most marked o v e r t h e f r e q u e n c y r a n g e 0 . 5 t o 2 Herz; r e s p o n s e s to added a c e t y l c h o l i n e (1 t o 5 0 ng/ml) were n o t s i g n i f i c a n t l y changed by metoclopramide. The p o s s i b i l i t y w a s i n v e s t i g a t e d t h a t metoclopramide was i n c r e a s i n g r e s p o n s e s t o c h o l i n e r g i c n e r v e s t i m u l a t i o n by b l o c k i n g e i t h e r i n h i b i t o r y n o r a d r e n e r g i c o r " p u r i n e r g i c " ( B u r n s t o c k , 1972) nervous e l e m e n t s a l s o a c t i v a t e d by f i e l d s t i m u l a t i o n . The s y m p a t h e t i c component of t h e f i e l d s t i m u l a t i o n r e s p o n s e s w e r e a b o l i s h e d by e i t h e r p h e n t o l a m i n e ( 1 t o 3 ug/ml) or b e t h a n i d i n e ( 1 t o 20 pg/ml) which r e s u l t e d i n a s m a l l i n c r e a s e i n t h e c o n t r a c t i l e r e s p o n s e s b u t d i d n o t p r e v e n t t h e u s u a l enhancement o f t h e r e s p o n s e s i n t h e p r e s e n c e o f...

Involvement of enteric neurones in the response of guinea‐pig ileum preparations to metoclopramide

“…Many observations concur that the drug facilitates spontaneous and stimulation-evoked release of acetylcholine (ACh) but a possible postjunctional sensitization of the smooth muscle cells to this neurotransmitter remains controversial Bianchi et al, 1970;Fontaine & Reuse, 1972;1973;Bury & Mashford, 1976;Anderson et al, 1977;Kilbinger et al, 1982;Zar et al, 1982;Massingham et al, 1985). Fox et al (1983) have recently demonstrated that surfactants can selectively ablate enteric neurones in the ratjejunum.…”